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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(3): 247-251, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36062794

RESUMO

Objective: To investigate the molecular mechanisms of Gupi Xiaoji decoction on apoptosis of human hepatoma cells HepG2. Methods: HepG2 cells were divided into 4 groups: control group (Control), blank serum group (Blank), Gupi Xiaoji Yin serum group (GPXJY) and cisplatin group (Positive). Eight duplicate holes were set in each group. After treated with Gupi Xiaoji Decoction-containing serum or cisplatin for 24 hours, the cell viability, the number of viable cells, the state of apoptosis, the cell cycle and the mitochondrial membrane potential were detected, and the level of lipid peroxidation (MDA) and glycolysis rate of the cells were detected. The expressions of apoptotic Bax, Bcl-2, and Caspase-3 proteins, and the contents of triacylglycerol (TG), cholesterol (TC), pyruvate and glucose in the cell supernatant were detected. Results: Compared with the control group, in the GPXJY group, the inhibition rate was increased (P<0.05), the number of cells was decreased, the number of apoptosis-positive cells was increased (P<0.01), the number of cells in the G1 phase was increased significantly (P<0.05), and the cell membrane potential was decreased (P<0.05,P<0.01), the glycolytic function was inhibited significantly, the MDA level was increased, the expressions of Bax and Caspase-3 in the GPXJY group were increased, and the expression of Bcl-2 was decreased (P<0.05, P<0.01). In cell supernatant, the TC, TG and glucose contents were decreased significantly, and the pyruvate content was increased significantly (P<0.05,P<0.01). Conclusion: Gupi Xiaoji Decoction can induce apoptosis of HepG2 cells and may play a role in energy metabolism.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Caspase 3/metabolismo , Cisplatino , Medicamentos de Ervas Chinesas , Glucose , Células Hep G2 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Piruvatos , Proteína X Associada a bcl-2/metabolismo
2.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4436-4445, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046873

RESUMO

This study aims to investigate the effect of atractylenolide Ⅲ(ATL-Ⅲ) on hydrogen peroxide(H_2O_2)-induced endoplasmic reticulum stress and apoptosis of H9 c2 cells via the ROS/GRP78/caspase-12 signaling pathway.The binding activity of ATL-Ⅲ to GRP78 was determined by molecular docking.The result showed that ATL-Ⅲ had a good binding activity to GRP78, and the binding activity of ATL-Ⅲ was stronger than that of its specific inhibitor.The endoplasmic reticulum stress model of H9 c2 was established by H_2O_2(100 µmol·L~(-1)) treatment.Five groups were designed: blank control group, model group, and ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) groups.Apoptosis was detected by Hoechst/PI double staining and flow cytometry.The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and lactate dehydrogenase(LDH) were measured by colorimetry.The levels of reactive oxygen species(ROS) and calcium(Ca~(2+)) in cytoplasm were determined by the fluorescence probe DCFH-DA and the calcium fluorescence probe Flou-4, respectively.The protein levels of GRP78, caspase-12, and caspase-3 were determined by Western blot, and the mRNA levels of GRP78 and caspase-12 by RT-qPCR.N-acetyl-L-cysteine(NAC) and 4-phenylbutyric acid(4-PBA) were respectively used to inhibit ROS and GRP78, and then the mechanism of ATL-Ⅲ in protecting the cells from endoplasmic reticulum stress induced by H_2O_2 were deduced.ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) decreased the apoptosis rate and ROS, MDA, and LDH levels(P<0.01), increased the SOD activity(P<0.01), and down-regulated the protein levels of GRP78, caspase-12, and caspase-3 and the mRNA levels of GRP78 and caspase-12(P<0.05).The addition of NAC decreased the apoptosis rate and ROS, MDA, GRP78, caspase-12, and caspase-3 levels(P<0.01), while it elevated the SOD level(P<0.01).The addition of 4-PBA also decreased the apoptosis rate and the levels of GRP78, caspase-12, caspase-3, and Ca~(2+)(P<0.01).The effect of inhibitors were consistent with that of ATL-Ⅲ.In conclusion, ATL-Ⅲ can protect H9 c2 cardiomyocytes by regulating ROS/GRP78/caspase-12 signaling pathway to inhibit H_2O_2-induced endoplasmic reticulum stress and apoptosis.


Assuntos
Cálcio , Chaperona BiP do Retículo Endoplasmático , Apoptose , Cálcio/farmacologia , Caspase 12/genética , Caspase 12/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Estresse do Retículo Endoplasmático , Lactonas , Simulação de Acoplamento Molecular , RNA Mensageiro , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos , Transdução de Sinais , Superóxido Dismutase/metabolismo
3.
Front Immunol ; 13: 956340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072579

RESUMO

Clostridioides difficile (C. difficile) produces toxins A (TcdA) and B (TcdB), both associated with intestinal damage and diarrhea. Pannexin-1 (Panx1) channels allows the passage of messenger molecules, such as adenosine triphosphate (ATP), which in turn activate the P2X7 receptors (P2X7R) that regulate inflammation and cell death in inflammatory bowel diseases. The aim of this study was to verify the effect of C. difficile infection (CDI) in the expression of Panx1 and P2X7R in intestinal tissues of mice, as well as their role in cell death and IL-6 expression induced by TcdA and TcdB in enteric glial cells (EGCs). Male C57BL/6 mice (8 weeks of age) were infected with C. difficile VPI10463, and the control group received only vehicle per gavage. After three days post-infection (p.i.), cecum and colon samples were collected to evaluate the expression of Panx1 by immunohistochemistry. In vitro, EGCs (PK060399egfr) were challenged with TcdA or TcdB, in the presence or absence of the Panx1 inhibitor (10Panx trifluoroacetate) or P2X7R antagonist (A438079), and Panx1 and P2X7R expression, caspase-3/7 activity and phosphatidylserine binding to annexin-V, as well as IL-6 expression were assessed. CDI increased the levels of Panx1 in cecum and colon of mice compared to the control group. Panx1 inhibitor decreased caspase-3/7 activity and phosphatidylserine-annexin-V binding, but not IL-6 gene expression in TcdA and TcdB-challenged EGCs. P2X7 receptor antagonist accentually reduced caspase-3/7 activity, phosphatidylserine-annexin-V binding, and IL-6 gene expression in TcdA and TcdB-challenged EGCs. In conclusion, Panx1 is increased during CDI and plays an important role in the effects of C. difficile toxins in EGCs, participating in cell death induced by both toxins by promoting caspase-3/7 activation via P2X7R, which is also involved in IL-6 expression induced by both toxins.


Assuntos
Toxinas Bacterianas , Clostridioides difficile , Conexinas , Proteínas do Tecido Nervoso , Receptores Purinérgicos P2X7 , Animais , Anexinas , Toxinas Bacterianas/metabolismo , Caspase 3/metabolismo , Morte Celular , Conexinas/genética , Conexinas/metabolismo , Mediadores da Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Fosfatidilserinas , Receptores Purinérgicos P2X7/genética
4.
Chin J Physiol ; 65(4): 199-208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36073568

RESUMO

Taurine is a free amino acid that prevents reactive oxygen species (ROS) formation. ROS production is associated with oxidative stress, cell proliferation, apoptosis, inflammation, and DNA alterations in benzo[α]pyrene (BaP)-induced lung cells. Here, we assessed the effect of adding of 25 mM taurine on human pulmonary alveolar epithelial A549 cells treated with different concentrations of BaP. After culturing for 24 h, the cells were tested for biomarkers including cell viability, cellular morphology, Annexin V-FITC/propidium iodide, cell cycle regulation, ROS accumulation, mitochondrial membrane potential (MMP), and expression of related signaling genes and proteins. BaP induced cell cycle arrest and decreased cell viability in a dose-dependent manner. In addition, 50 µM BaP induced a 52.2% increase in ROS levels and inhibited MMP by up to 80%; however, taurine decreased BaP-induced ROS production by 19.5% and restored MMP. The expression of nuclear factor-kappa B (NF-κB), B-cell lymphoma-2 (BCL-2) homologous antagonist killer (Bak), BCL-2-associated X protein (Bax), and cytochrome c at both the mRNA and protein levels were increased, and the expression of BCL-2 and BCL-x1 was decreased by BaP treatment. Furthermore, BaP activated caspase-3/7 expression by up to 25%. However, taurine decreased the expression of NF-κB, Bak, Bax and cytochrome c levels, reduced caspase-3/7 activities, and increased the expression of BCL-2 and BCL-x1. Hence, taurine attenuates BaP-induced oxidative stress and mitochondrial dysfunction by inhibiting the NF-κB-mediated intrinsic apoptosis pathway in A549 cells. Taurine can be considered as a preventive molecule to prevent lung damage.


Assuntos
Benzo(a)pireno , NF-kappa B , Células A549 , Apoptose , Benzo(a)pireno/toxicidade , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular , Citocromos c/metabolismo , Humanos , Mitocôndrias , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taurina/farmacologia , Proteína X Associada a bcl-2/metabolismo
5.
Artigo em Chinês | MEDLINE | ID: mdl-36052583

RESUMO

Objective: To investigate the protective effect and mechanism of Nicotinamide Riboside (NR) on lung injury caused by Paraquat intoxicated mice. Methods: Eighty clean male BALB/C mice were selected and averagely divided forty mice into 4 groups with 10 mice in each group, PQ group was given 25% PQ solution (60 mg/kg) by one-time gavage. PQ+NR group were intraperitoneally injected with NR solution (300 mg/kg) 1 hour before given the same amount of PQ solution (60 mg/kg) by one-time gavage, The Control group were given the same amount of saline by one-time gavage, The same amount of NR was intraperitoneally injected before NR group were given saline by one-time gavage. Observed and recorded general condition of PQ intoxicated mice. Observed and recorded the death of mice every half an hour and counted the mortality and drew survival curve of each group after 72 hours exposure. another forty mice were averagely divided and treated by the same way. After 24 hours of modelling, mice were anaesthetized and killed. Then blood was extracted after eyeball was removed. The changes of TNF-a、IL-6 and MPO in serum of mice were detected by ELISA.Two lung tissues were removed from the chest and used to measure the D/W ratio of the lung. The pathological changes of lung were observed and scored under light microscope.The levels of SOD, MDA and Caspase-3 in lung tissues were determined by chemical colorimetry. The expression of Sirt1 and Nrf2 in lung tissues was detected by Western-blot. Results: Compared with the Control group and the NR group, the mice in the PQ group had a poor general condition, such as depression, crouching, skin disorder and reduced activity, food, urine and feces. The symptoms in the PQ+NR group were reduced compared with the PQ group. The survival rate at 72 hours after exposure: 80% in the PQ+NR group and 40% higher than that in the PQ group (P=0.029) . Compared with Control group and NR group, the D/W ratio (0.09±0.07) , lung pathology score under light microscope (11.80±0.37) , TNF-a (39.89±1.48) pg/ml、IL-6 (77.29±2.38) pg/ml、MPO (0.31±0.01) µg/ml、SOD (6.62±0.30) U/mgprot、MDA level (1.21±0.14) mmol/mgprot, Caspase-3 activity (356.00± 27.16) %, Sirt1 and Nrf2 protein expression (1.02±0.14、0.82±0.06) were significantly decreased in PQ group (P=0.004、0.023) ; Compared with PQ group, PQ+NR group significantly increased the D/W ratio (0.10±0.10) , decreased the pulmonary pathology score under light microscope (7.400.51) , decreased TNF-a (33.00± 0.65) pg/ml、IL-6 (52.23±4.23) pg/ml、MPO leve (0.23±0.01) µg/mll, increased SOD leve (9.28±0.45) U/mgprotl, decreased MDA level (0.78±0.02) mmol/mgprot, decreased Caspase-3 activity (222.80±7.59) %, and increased the protein expressions of Sirt1 and Nrf2 (1.62±0.16、1.06±0.04) (P=0.048、0.035) . Conclusion: NR can prolong the survival time of PQ poisoned mice; NR intervention can effectively inhibit the inflammatory response, peroxidation injury and apoptosis of PQ poisoned mice; NR intervention can upregulate the expression of Sirt1 and Nrf2 protein and effectively reduce the lung injury of PQ poisoning.


Assuntos
Lesão Pulmonar , Niacinamida , Paraquat , Compostos de Piridínio , Animais , Caspase 3/metabolismo , Interleucina-6/metabolismo , Pulmão , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Paraquat/toxicidade , Compostos de Piridínio/farmacologia , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo
6.
Pharm Biol ; 60(1): 1781-1789, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36102594

RESUMO

CONTEXT: Polyphyllin II (PPII) is a steroidal saponin isolated from Rhizoma Paridis. It exhibits significant antitumor activity such as anti-proliferation and pro-apoptosis in lung cancer. OBJECTIVE: To explore whether PPII induce autophagy and the relationship between autophagy and apoptosis in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: The effects of PPII (0, 1, 5, and 10 µM) were elucidated by CCK8 assay, colony formation test, TUNEL staining, MDC method, and mRFP-GFP-LC3 lentivirus transfection in A549 and H1299 cells for 24 h. DMSO-treated cells were selected as control. The protein expression of autophagy (LC3-II, p62), apoptosis (Bcl-2, Bax, caspase-3) and p-mTOR was detected by Western blotting. We explored the relationship between autophagy and apoptosis by autophagy inhibitor CQ (10 µM) and 3-MA (5 mM). RESULTS: PPII (0, 1, 5, and 10 µM) inhibited the proliferation and induced apoptosis. The IC50 values of A549 and H1299 cells were 8.26 ± 0.03 and 2.86 ± 0.83 µM. We found that PPII could induce autophagy. PPII promoted the formation of autophagosome, increased the expression of LC3-II/LC3-I (p < 0.05), while decreased p62 and p-mTOR (p < 0.05). Additionally, the co-treatment with autophagy inhibitors promoted the protein expression of c-caspase-3 and rate of Bax/Bcl-2 (p < 0.05), compared with PPII-only treatment group. Therefore, our results indicated that PPII-induced autophagy may be a mechanism to promote cell survival, although it can also induce apoptosis. CONCLUSIONS: PPII-induced apoptosis exerts its anticancer activity by inhibiting autophagy, which will hopefully provide a prospective compound for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Saponinas , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/farmacologia , Transdução de Sinais , Esteroides , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2
7.
Pharm Biol ; 60(1): 1751-1761, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36102631

RESUMO

CONTEXT: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. OBJECTIVE: Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism. MATERIALS AND METHODS: UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 µM), ATS (40 µM), UA (5 µM) + ATS (40 µM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. RESULTS: The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 µM) + ATS (ED50: 40 µM) could protect H2O2-induced (IC50: 250 µM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. CONCLUSIONS: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.


Assuntos
Fármacos Neuroprotetores , Proteínas Proto-Oncogênicas c-akt , Animais , Caspase 3/metabolismo , Glucosídeos , Peróxido de Hidrogênio/toxicidade , Farmacologia em Rede , Fármacos Neuroprotetores/farmacologia , Ácido Oleanólico/análogos & derivados , Células PC12 , Polifenóis , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
8.
Biomed Res Int ; 2022: 5940372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093409

RESUMO

Ganoderic acid A (GAA) exhibited neuron protection in in vitro epilepsy study, but no study has been done in vivo. Rats were administered (i.p.) pentylenetetrazole daily for 28 days to induce seizure. Rats with grade II or above of epileptic score were divided into three groups and given placebo, sodium valproate, or GAA treatment, respectively, for 7 days. The electrical signals of brain were monitored with electroencephalography (EGG); epileptic behavior was assessed using the Racine scale; morphological changes and apoptosis rate of cortical neurons were assessed with H&E staining and TUNEL staining, respectively. Protein expression of calcium-sensing receptor, p-ERK, p-JNK, and p-p38 in hippocampal tissue and Bcl-2, cleaved caspase-3, and Bax in cortical tissues was observed by Western blot and immunohistochemistry assay, respectively. After GAA treatment, apparent seizure-like EEG with significant arrhythmic disorder and spike waves was reduced or disappeared, and wave amplitude of EEG was reduced significantly. GAA showed similar effect with sodium valproate treatments on epilepsy. There were an apparent improvement of the epileptic behavior and a significant increase in the epileptic latency and shortening of the epileptic duration in the treatment group compared to control. GAA treatment ameliorated the nuclear pyknosis of neurons which appeared seriously in the epilepsy group. GAA treatment significantly reduced the cortical neuron apoptosis of epilepsy and the expression of calcium-sensing receptor, p-P38, p-JNK, cleaved caspase-3, and Bax but increased the expression of both p-ERK and Bcl-2. In conclusion, GAA treatment showed strong antiepileptic effect by decreasing apoptosis in cortical neuron and the expression of calcium-sensing receptor and stimulating the MAPK pathway.


Assuntos
Epilepsia , Pentilenotetrazol , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Caspase 3/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Ácidos Heptanoicos , Lanosterol/análogos & derivados , Pentilenotetrazol/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Receptores de Detecção de Cálcio , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Ácido Valproico/efeitos adversos , Proteína X Associada a bcl-2/metabolismo
9.
PLoS One ; 17(9): e0274607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36108271

RESUMO

Mesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-ß, SMAD, Snail, Slug, ß-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Neoplasias do Colo do Útero , Geleia de Wharton , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Portadores de Fármacos/metabolismo , Exossomos/metabolismo , Feminino , Células HeLa , Humanos , Células-Tronco Mesenquimais/metabolismo , Paclitaxel/metabolismo , Paclitaxel/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Geleia de Wharton/metabolismo , Proteína X Associada a bcl-2/metabolismo , beta Catenina/metabolismo
10.
Oxid Med Cell Longev ; 2022: 2297268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120597

RESUMO

Objective: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods: Forty db/db mice with diabetes (random blood glucose ≥ 250 mg/dL) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results: Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion: Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose , Glicemia , Caspase 3/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse do Retículo Endoplasmático , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Hepatócitos/metabolismo , Hipoglicemiantes/farmacologia , Lipídeos , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Superóxido Dismutase-1/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
Physiol Rep ; 10(18): e15468, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36117389

RESUMO

Meprin metalloproteinases have been implicated in the pathophysiology of ischemia/reperfusion (IR)-induced kidney injury. Previous in vitro data showed that meprin ß proteolytically processes interleukin-6 (IL-6) resulting in its inactivation. Recently, meprin-ß was also shown to cleave the IL-6 receptor. The goal of this study was to determine how meprin ß expression impacts IL-6 and downstream modulators of the JAK2-STAT3-mediated signaling pathway in IR-induced kidney injury. IR was induced in 12-week-old male wild-type (WT) and meprin ß knockout (ßKO) mice and kidneys obtained at 24 h post-IR. Real-time PCR, western blot, and immunostaining/microscopy approaches were used to quantify mRNA and protein levels respectively, and immunofluorescence counterstaining with proximal tubule (PT) markers to determine protein localization. The mRNA levels for IL-6, CASP3 and BCL-2 increased significantly in both genotypes. Interestingly, western blot data showed increases in protein levels for IL-6, CASP3, and BCL-2 in the ßKO but not in WT kidneys. However, immunohistochemical data showed increases in IL-6, CASP3, and BCL-2 proteins in select kidney tubules in both genotypes, shown to be PTs by immunofluorescence counterstaining. IR-induced increases in p-STAT-3 and p-JAK-2 in ßKO at a global level but immunoflourescence counterstaining demonstrated p-JAK2 and p-STAT3 increases in select PT for both genotypes. BCL-2 increased only in the renal corpuscle of WT kidneys, suggesting a role for meprins expressed in leukocytes. Immunohistochemical analysis confirmed higher levels of leukocyte infiltration in WT kidneys when compared to ßKO kidneys. The present data demonstrate that meprin ß modulates IR-induced kidney injury in part via IL-6/JAK2/STAT3-mediated signaling.


Assuntos
Interleucina-6 , Traumatismo por Reperfusão , Animais , Caspase 3/metabolismo , Interleucina-6/metabolismo , Isquemia/metabolismo , Rim/metabolismo , Masculino , Metaloendopeptidases , Metaloproteases/metabolismo , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Receptores de Interleucina-6/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
12.
Mediators Inflamm ; 2022: 2356507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117589

RESUMO

Ischemic stroke (IS) is a general term for necrosis of brain tissue caused by stenosis, occlusion of arteries supplying blood to the brain (carotid artery and vertebral artery), and insufficient blood supply to the brain. Cerebral ischemia is the main kind of IS causing cell damage. However, the underlying mechanism still needs to be clarified further. In this study, it was demonstrated that FFAR1 was a hub gene in IS. The expression of FFAR1 was increased in PC12 cells with OGD/R treatment. FFAR1 deficiency inhibited cell viability and induced cell apoptosis, which was reversed by FFAR1 overexpression. Moreover, candesartan, as a compound targeting FFAR1, facilitated cell viability and reduced cell apoptosis. The expression of ITGA4 was also high in OGD/R-PC12 cells as FFAR1. Furthermore, FFAR1 deficiency retarded the increasing of cell viability and inhibition of cell apoptosis by downregulation of Bax and Cleaved Caspase-3 in OGD/R-PC12 cells with candesartan treatment. In conclusion, candesartan may regulate neuronal apoptosis through FFAR1/ITGA4 axis.


Assuntos
AVC Isquêmico , Animais , Apoptose/fisiologia , Benzimidazóis , Compostos de Bifenilo , Caspase 3/metabolismo , Glucose/metabolismo , Oxigênio/metabolismo , Ratos , Tetrazóis , Proteína X Associada a bcl-2
13.
Comput Math Methods Med ; 2022: 1949344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118839

RESUMO

Alzheimer's disease (AD) is the most commonly seen neurodegenerative brain disorder. The paracrine effects of mesenchymal stem cells (MSCs) signify to trigger immunomodulation and neural regeneration. However, the role and mechanism of bone marrow MSC- (BMSC-) derived CX3CL1 in AD remains elusive. In this study, Aß 1-42-intervened SH-SY5Y cells were used for AD cell model construction. pcDNA-ligated CX3CL1 overexpression plasmids were transfected into BMSCs. The levels of soluble and membrane-bound CX3CL1 were detected by ELISA and Western blotting (WB), respectively. The growth, apoptosis, and pathology of AD model cells were evaluated by CCK-8, flow cytometry, immunofluorescence, morphology observation, biochemical examination, and WB. It was found that Aß 1-42 significantly reduced CX3CL1 expression either in soluble or membrane-bound form, cell viability, relative protein expression of synaptic markers, SOD, CAT, and GSH-Px contents, as well as Trx protein expression; in addition, it enhanced the apoptosis rate, the relative expression of cleaved caspase-3, Aß, tau, p-Tau, Iba1, MDA, TXNIP, and NLRP3 in SH-SY5Y cells; however, the above effects were prominently reversed by the coculture of BMSCs. Moreover, overexpression of CX3CL1 in BMSCs observably strengthened the corresponding tendency caused by BMSCs. In conclusion, through the TXNIP/NLRP3 pathway, CX3CL1 derived from BMSCs inhibited pathological damage in Aß 1-42-induced SH-SY5Y.


Assuntos
Doença de Alzheimer , Células-Tronco Mesenquimais , Neuroblastoma , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Caspase 3/metabolismo , Caspase 3/farmacologia , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/farmacologia , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Sincalida/metabolismo , Sincalida/farmacologia , Superóxido Dismutase
14.
Tissue Cell ; 78: 101898, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36049371

RESUMO

Individuals with Down syndrome (DS) exhibit impaired olfactory function and are at a higher risk of developing Alzheimer's disease (AD). Olfactory dysfunction may be an early clinical symptom of AD. Recent studies have demonstrated that vitamin D3 (VD3) exerts neuroprotective effects in mouse models of AD. In this study, we investigated the effects of VD3 on the morphology, immunolocalization, and markers involved in neuropathogenic processes, apoptosis, proliferation, cell survival, and clearance of amyloid peptides, along with neuronal markers in the olfactory bulb (OB) of an adult female mouse model of DS. Morphological and molecular analyses revealed that trisomic mice exhibited a volume reduction in the external plexiform layer, a decrease in the number of mitral and granule cells, and an increase in the expression of amyloid-ß 42, caspase-3 p12, and P-glycoprotein. VD3 reversed certain morphological abnormalities in the OB of control trisomic mice (Ts(CO)) and decreased the levels of caspase-3 p12 and methylenetetrahydrofolate reductase in the treated groups. The results demonstrated that trisomy factor causes morphofunctional abnormalities in the OB of Ts(CO) mice. Moreover, VD3 could represent a therapeutic target to attenuate morphological and molecular alterations in OB.


Assuntos
Doença de Alzheimer , Síndrome de Down , Fármacos Neuroprotetores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Animais , Caspase 3/metabolismo , Colecalciferol/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Síndrome de Down/tratamento farmacológico , Síndrome de Down/genética , Síndrome de Down/metabolismo , Feminino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Camundongos , Camundongos Transgênicos , Bulbo Olfatório/metabolismo
15.
Environ Mol Mutagen ; 63(6): 286-295, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36053843

RESUMO

In this study, the neuroprotective action potential by ulexite (UX) (18.75 mg/L) against acetylferrocene (AFC) (3.82 mg/L) induced neurotoxicity was aimed to investigate in brain tissues of Oncorhynchus mykiss. For this purpose, the effects on neurotoxicity markers, proinflammatory cytokines, antioxidant immune system, DNA, and apoptosis mechanisms were assessed on brain tissues in the 48-96  h of the 96- trial period. In this research, it was determined that brain-derived nerve cell growth factor (BDNF) level and acetylcholinesterase (AChE) activity were inhibited in the brain tissue compared to the control group by AFC. In addition, inhibition in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) values (which are antioxidant system biomarkers), and inductions in malondialdehyde (MDA) and myeloperoxidase (MPO) amounts (which are indicators of lipid peroxidation) were determined (p < 0.05) after exposure to AFC. And, while tumor necrosis factor-α (TNF-α) and IL-6 levels were increased in the AFC-exposed group, Nrf-2 levels were found to be remarkably decreased. Upregulation was also detected in 8-hydroxydeoxyguanosine (8-OHdG) and caspase-3 levels, which are related to DNA damage and apoptosis mechanism. On the contrary, UX (single/with AFC) suppressed the AChE and BDNF inhibition by AFC. Moreover, UX mitigated AFC-induced oxidative, inflammatory, and DNA damage and attenuated AFC-mediated neurotoxicity via activating Nrf2 signaling in fish. Collectively, our findings revealed that UX supplementation might exert beneficial effects and may be considered as a natural and promising neuroprotective agent against AFC-induced toxicity.


Assuntos
Fármacos Neuroprotetores , Oncorhynchus mykiss , 8-Hidroxi-2'-Desoxiguanosina , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Caspase 3/metabolismo , Caspase 3/farmacologia , Catalase/metabolismo , Compostos Ferrosos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/farmacologia , Interleucina-6/metabolismo , Malondialdeído , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Peroxidase/metabolismo , Peroxidase/farmacologia , Superóxido Dismutase , Fator de Necrose Tumoral alfa
16.
Gene ; 845: 146854, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36055605

RESUMO

Mesenchymal stem cells (MSCs) have pluripotent differentiation ability and play an important role in human clinical cell therapy. While, the research on MSCs in endangered wild animals is extremely rare. In our previous studies, the bone marrow mesenchymal stem cells (bmMSCs) and umbilical cord mesenchymal stem cells (ucMSCs) of giant panda (Ailuropoda melanoleuca) were successfully isolated. We aimed to characterize the differences in gene expression profiles between these two types of MSCs using RNA sequencing (RNA-Seq) and to determine which potential pathways are involved in functional regulation. In total, 1079 significantly differentially expressed genes (DEGs) were identified, of which 478 genes were upregulated and 601 genes were downregulated. The significantly enriched Gene Ontology (GO) terms mainly contained cell adhesion, biological adhesion, intracellular signal transduction, molecular function regulator, Ras protein signal transduction, small GTPase mediated signal transduction, and regulation of Rho protein signal transduction. The most enrichment pathways of DEGs enriched in Kyoto Encyclopedia of Genes Genomes (KEGG) were PI3K-AKT signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, Hippo signaling pathway, Wnt signaling pathway, cGMP-PKG signaling pathway and Signaling pathways regulating pluripotency of stem cells. In addition, quantitative real time polymerase chain reaction (qRT-PCR) showed that the AKT3, CDK2, MAPK3, mTOR, PI3K and PTK2 genes associated with PI3K-AKT pathway were highly expressed (P < 0.01), and Caspase-3 was low expressed (P < 0.05) in ucMSCs group when compared with bmMSCs. After treatment with the PI3K inhibitor LY294002, genes AKT3, CDK2, MAPK3, mTOR, and PTK2 were significantly decreased in ucMSCs (P < 0.01), and Caspase-3 was significantly up regulated (P < 0.001). In conclusion, we for the first time compared and analyzed the transcriptome profiles of giant panda ucMSCs and bmMSCs, and found the PI3K-AKT pathway was highly activated and might be a key signaling pathway in the ucMSCs regulation. This study will be beneficial for the research on MSCs proliferation regulation and differentiation of giant pandas in the future, and lay the foundation for MSCs application and clinical therapy for endangered wild animals.


Assuntos
Células-Tronco Mesenquimais , Proteínas Monoméricas de Ligação ao GTP , Ursidae , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Caspase 3/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transcriptoma , Cordão Umbilical , Ursidae/genética , Proteínas ras
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(9): 801-806, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36082710

RESUMO

Objective To explore the role of microRNA-488-3p (miR-488-3p) in podocytes apoptosis induced by homocysteine (Hcy). Methods Flow cytometry was employed to analyze the ratio of podocytes apoptosis after treated with 0 µmol/L Hcy (control group) or 80 µmol/L Hcy (Hcy group) for 48 hours. The expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-related X protein (BAX), and caspase-3 were measured by Western blot analysis in podocytes, after cells were treated with 80 µmol/L Hcy (Hcy group) for 48 hours, and the expression of miR-488-3p was detected by real-time PCR. The transfection and apoptosis ratio of podocytes were also detected after cells were transfected with miR-488-3p inhibitor. Results The apoptosis rate of podocytes increased in cells treated with Hcy, compared with control group. The expression levels of BAX and caspase-3 increased significantly in Hcy group, while Bcl2 expression was suppressed by Hcy. Furthermore, the expression of miR-488-3p increased in Hcy-induced podocyte. On the contrary, podocyte showed an decreased apoptosis rate, expression levels of BAX and caspase-3 decreased after cells were transfected with miR-488-3p inhibitor. However, Bcl2, which was not in this line, showed an increase when the cells transfected with miR-488-3p inhibitor. Conclusion Hcy promotes apoptosis of podocyte by up-regulating the expression of miR-488-3p.


Assuntos
Apoptose , Homocisteína , MicroRNAs , Podócitos , Animais , Caspase 3/genética , Caspase 3/metabolismo , Homocisteína/farmacologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Regulação para Cima , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
18.
Clinics (Sao Paulo) ; 77: 100076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36088885

RESUMO

OBJECTIVES: This study aims to explore the effect of silencing Beclin-1 gene on autophagy and apoptosis of Benign Prostatic Hyperplasia (BPH) (BPH-1) cells under the condition of Androgen Deprivation (AD) and Autophagy Inhibition (AI). METHODS: Control group (BPH-1 group), empty carrier group (sh-RNA-BPH-1 group) and Beclin-1 silenced group (sh-Beclin1-BPH-1 group) were set. The Beclin-1 gene silencing efficiency was detected by RT-PCR and Western blot. Autophagic flux was monitored by GFP-LC3 cleavage assay and cell apoptosis was analyzed by flow cytometry. The protein expression levels of LC3, Caspase-3, PARP-1, Bcl-2, and Bax were detected by Western blot. RESULTS: The transfection of sh-Beclin-1 obviously down-regulated the expression of Beclin-1 at both mRNA and protein levels. Under the conditions of AD and AI, silencing of Beclin-1 restrained the autophagy of BPH-1 cells, as evidenced by a decreased number of autophagosomes and down-regulation of LC3-II protein (p < 0.001). The results of flow cytometry showed that the apoptotic rate of sh-Beclin-1 group was elevated significantly compared to the other two groups (p < 0.01). Western blot results showed that silencing of Beclin-1 promoted 89 kd fragmentation of PARP-1 (p < 0.001) and Caspase-3 activation (p < 0.01). Moreover, silencing of Beclin-1 resulted in declined Bcl-2 and augmented Bax protein expression in BPH-1 cells (p < 0.01), which ultimately led to a decreased Bcl-2/Bax ratio. CONCLUSIONS: The results indicated that the silencing of Beclin-1 gene hampered autophagy while activating apoptosis in BPH-1 cells. Thus, Beclin-1 may participate in an antagonistic relationship between autophagy and apoptosis in BPH.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Antagonistas de Androgênios , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/farmacologia , Autofagia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Caspase 3/farmacologia , Células Epiteliais/metabolismo , Inativação Gênica , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
19.
Proc Natl Acad Sci U S A ; 119(38): e2205454119, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36095190

RESUMO

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but often patients develop acquired resistance. Although other agents are in clinical use to treat trastuzumab-resistant (TR) breast cancer; still, the patients develop recurrent metastatic disease. One of the primary mechanisms of acquired resistance is the shedding/loss of the HER2 extracellular domain, where trastuzumab binds. We envisioned any new agent acting downstream of the HER2 should overcome trastuzumab resistance. The mixed lineage kinase 3 (MLK3) activation by trastuzumab is necessary for promoting cell death in HER2+ breast cancer. We designed nanoparticles loaded with MLK3 agonist ceramide (PPP-CNP) and tested their efficacy in sensitizing TR cell lines, patient-derived organoids, and patient-derived xenograft (PDX). The PPP-CNP activated MLK3, its downstream JNK kinase activity, and down-regulated AKT pathway signaling in TR cell lines and PDX. The activation of MLK3 and down-regulation of AKT signaling by PPP-CNP induced cell death and inhibited cellular proliferation in TR cells and PDX. The apoptosis in TR cells was dependent on increased CD70 protein expression and caspase-9 and caspase-3 activities by PPP-CNP. The PPP-CNP treatment alike increased the expression of CD70, CD27, cleaved caspase-9, and caspase-3 with a concurrent tumor burden reduction of TR PDX. Moreover, the expressions of CD70 and ceramide levels were lower in TR than sensitive HER2+ human breast tumors. Our in vitro and preclinical animal models suggest that activating the MLK3-CD70 axis by the PPP-CNP could sensitize/overcome trastuzumab resistance in HER2+ breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/patologia , Ligante CD27/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Ceramidas , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , MAP Quinase Quinase Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab/metabolismo , Trastuzumab/farmacologia
20.
Contrast Media Mol Imaging ; 2022: 5132691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082059

RESUMO

Objective: To explore the effect of the Wnt/ß-catenin signaling pathway on the proliferation and apoptosis of gastric cancer cells. Methods: An MTT colorimetric assay was used to detect the inhibitory effect of the Wnt/ß-catenin signaling pathway inhibitor FH535 on the proliferation of MKN45 gastric cancer cells. The cell proliferation index (PI) and apoptosis index (AI) were measured by flow cytometry. The expression levels of ß-catenin, c-myc, and cleaved caspase-3 in MKN45 gastric cancer cells were detected. Results: After using the Wnt/ß-catenin signaling pathway inhibitor FH535, MKN45 gastric cancer cells showed obvious shrinkage, death, and cell density decrease. MTT showed that the A value of MKN45 gastric cancer cells in FH535 group was significantly lower than that in the control group (P < 0.05). The survival rate of MKN45 gastric cancer cells in FH535 group was significantly lower than that in the control group (P < 0.05). The cell cycle of gastric cancer was arrested in G0/G1 phase. The expression levels of ß-catenin and c-myc protein in MKN45 gastric cancer cells in FH535 group decreased significantly (P < 0.05), while the expression level of cleaved caspase-3 protein increased significantly (P < 0.05). Conclusion: The Wnt/ß-catenin signal molecule can maintain the proliferation of gastric cancer cells. Inhibition of the Wnt/ß-catenin signaling pathway can inhibit the proliferation of gastric cancer cells and promote the apoptosis of MKN45 gastric cancer cells.


Assuntos
Neoplasias Gástricas , Via de Sinalização Wnt , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , beta Catenina/metabolismo , beta Catenina/farmacologia
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