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1.
Adv Exp Med Biol ; 1280: 231-241, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791986

RESUMEN

Although normal cells depend on exogenous lipids to function and survive, excessive amount of body fat has been associated with increased risk for certain human cancers. Cancer cells can redirect metabolic pathways to meet energy demands through the regulation of fatty acid metabolism. The importance of de novo fatty acid synthesis and fatty acid oxidation in cancer cells suggests fatty acid metabolism may be targeted for anticancer treatment through the use of pharmacological blockade to limit cell proliferation, growth, and transformation. However, our current knowledge about fatty acid metabolism in cancer cells remains limited, and the investigations of such processes and related pathways are certainly warranted to reveal the clinical relevance of fatty acid metabolism in cancer diagnosis and therapy.


Asunto(s)
Ácidos Grasos , Neoplasias , Proliferación Celular , Metabolismo Energético , Humanos , Metabolismo de los Lípidos , Lípidos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 363-368, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812400

RESUMEN

OBJECTIVE: To investigate the effect of Bmi-1 expression on the chemosensitivity of THP-1 cells and its relative mechanism. METHODS: The pGenesil-2-Bmi-1 1 siRNA, p-MSCV-Bmi-1 plasmid was transfected into THP-1 cells to reduce or increase the expression of Bmi-1. The expression of Bmi-1 mRNA and protein was verified by PCR and Western blot. The effect of camptothecin (CPT) on the proliferation and chemosensitivity of THP-1 cells affected by Bmi-1 gene were detected by MTT assay. The expression of DNA double-strand breaks marker-γ-H2AX was detected by immunofluorescence assay. Mitochondrial membrane potential and apoptosis were observed by flow cytometry. The expression of Cytochrome C, Caspase 3, Bax and BCL-2 was detected by Western blot. RESULTS: Silencing Bmi-1 could inhibit proliferation and enhance the sensitivity of THP-1 cells to CPT, while overexpressed Bmi-1 could promote the cell proliferation and attenucate sensitivity of THP-1 cells to CPT. Silencing Bmi-1 could enhance CPT-induced DNA double-strand breaks, decrease mitochondrial membrane potential and promote CPT-induced apoptosis. While increasing Bmi-1 gene expression could attenuate CPT-induced DNA double-strand breaks, enhamce mitochondrial membrane potential and significantly reduce CPT-induced apoptosis of cells. CONCLUSION: Bmi-1 expression could influence the sensitivity of THP-1 cells to CPT, and its relative mechanism may relate to DNA double-strand breaks and endogenous apoptotic pathways.


Asunto(s)
Apoptosis , Camptotecina , Camptotecina/farmacología , Línea Celular Tumoral , Proliferación Celular , Células THP-1
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 381-388, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812403

RESUMEN

OBJECTIVE: The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-ß) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell. METHODS: Cell proliferation inducing rate of FA-2-b-ß to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-ß performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8. RESULTS: The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-ß, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-ß as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-ß. CONCLUSION: FA-2-b-ß is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.


Asunto(s)
Agaricales , Leucemia Mielógena Crónica BCR-ABL Positiva , Animales , Apoptosis , Proliferación Celular , Humanos , Células K562 , Ratones
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 389-394, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812404

RESUMEN

OBJECTIVE: To investigate the effects of recombinant human thrombopoietin (rhTPO) to proliferation and apoptosis of acute myeloid leukemia (AML) cell lines. METHODS: After the treatment of different concentrations of rhTPO (0, 50, 100 ng/ml) for different time (24,48,72 h),the cell proliferation rates of the AML cell lines (Kasumi-1, Skno-1, HEL, HL-60, THP-1) were determined by CCK-8 method. Apoptosis rate of each cell line cocultured with rhTPO was detected by Annexin V/PI method. The relative expression of TPO receptor c-MPL (myeloproliferative clonal antibody) mRNA in AML cell lines was detected by Q-PCR. The expression of c-MPL protein in each cell line was detected by Western blot. The expression of c-MPL antigen in HL-60 cells treated by different concentrations of rhTPO was detected by Flow cytometry. RESULTS: RhTPO showed no promotion to the proliferation of Kasumi-1, Skno-1, HEL, HL-60, THP-1 cell lines,however,it showed inhibitory effect to cell proliferation (72 h 0 ng/ml vs 100 ng/ml, P= 0.029) and pro-apoptotic (48 h 0 ng/ml vs 50 ng/ml, P=0.0143) in HL-60 cells. In Kasumi-1, Skno-1, HEL and THP-1 cells, there showed no statistically significant differences in apoptosis rate among each groups treated by different concentrations of rhTPO. Each AML cell line showed different levels of c-MPL gene and c-MPL protein expression, but HEL cells showed the highest expression in both of them. After HL-60 cells were treated by different concentrations of rhTPO for 48 hours, there showed no statistical difference in c-MPL antigen expression among each groups. CONCLUSION: RhTPO can not promote the proliferation of Kasumi-1, Skno-1, HEL, HL-60 and THP-1 leukemia cell lines. On the contrary, rhTPO can inhibit HL-60 cell proliferation and promote its apoptosis, and this effect is not related to c-MPL gene expression or protein expression.


Asunto(s)
Leucemia Mieloide Aguda , Trombopoyetina , Apoptosis , Proliferación Celular , Humanos , Proteínas de Neoplasias , Proteínas Proto-Oncogénicas , Receptores de Citocinas
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 408-415, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812407

RESUMEN

OBJECTIVE: To investigate the influence of GPT2(glutamic pyruvate transaminase 2)to biological characteristics of human acute myeloid leukemia cell line HL-60. METHODS: The expression of GPT2 in hematological tumor and AML cell was detected. The lentvirus-mediated of short-hairpin RNA (shRNA) was constricted, and the knock-down efficiency of HL-60 in AML cell after infected by lentvirus-mediated was detected by Western blot and Q-PCR. CCK-8 assay and soft agar colony formation assay were used to detect the effect of GPT2 gene deletion to the cell proliferation potential. Fluorescence activated cell sorting(FACS) was used to analyze the effect of gene deletion to the cell cycle and Caspase 3/7 Activity Assay Kit was used to analyze the effect of GPT2 gene deletion to the cell apoptosis. RESULTS: GPT2 showed mRNA high expression in AML patients. CCK-8, soft agar assay, and Caspase 3/7 Activity Assay Kit results showed that compared with shCtrl group, the cells in shGPT2-1、shGPT2-2、shGPT2-3 group showed the slowing down on proliferation, decreasing on colony ability, and the apoptosis of the cells was increasing significantly. FACS showed that GPT2 gene was related to the cycle of HL-60 cell. CONCLUSION: GPT2 appears to involve the proliferation, cycle distribution and apoptosis of AML cell HL-60. The deletion of GPT gene can lead to the inhibitation of cells proliferation and increase apoptosis.


Asunto(s)
Leucemia Mieloide Aguda , Apoptosis , Proliferación Celular , Células HL-60 , Humanos , Piruvatos , Transaminasas
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 422-427, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812409

RESUMEN

OBJECTIVE: To investigate the effect of tumor necrosis factor death receptor (DR) 4 demethylation to the proliferation and apoptosis of myeloid leukemia K562 cells. METHODS: The logarithmic phase of K562 cells were treated by desitabine (DCA) at 0, 0.8, 1.6 and 3.2 µmol/L, and the cells were divided into control group, DCA low dose group, DCA medium dose group and DCA high dose group respectively. The cells in control group were treated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) 0.5 µg/ml for 24 h, and the cells were divided into TRAIL group. The cells in DCA high dose group were treated by TRAIL 0.5 µg/ml for 24 h, and were divided into DCA high dose + TRAIL group. Methylation-specific polymerase chain reaction (MS-PCR) was used to measure the methylation status of the DR4 gene promoter in the control group and DCA low, medium and high dose groups. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to determine the relative expression of DR4 mRNA and protein in the control group and DCA low, medium and high dose groups. Dime- thylthiazole (MTT) method was used to determine the inhibition rate of cell proliferation of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. Flow cytometry was used to determine the apoptotic rate of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. RESULTS: The cells in the control group were methylation-positive, the brightness of the methylation bands of the cells in the DCA low, medium, and high dose groups was gradually decreased to disappear, and the DCA high dose group showed negative for methylation. The relative expression of DR4 mRNA and protein in the control group, DCA low, medium and high dose groups was increased sequentially (r=0.624, 0.704). The inhibition rate of cell proliferation of the cells in the control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group was increased sequentially (r=0.653, 0.754, 0.709, 0.725) at 24, 48 and 72 h. CONCLUSION: DCA can reverse the methylation level of DR4 gene promoter in ML K562 cells and up-regulate the expression of DR4, which may enhance the proliferation inhibition and apoptosis promotion effects of TRAIL on K562 cells.


Asunto(s)
Leucemia Mieloide , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Desmetilación , Humanos , Células K562 , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 489-493, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812419

RESUMEN

OBJECTIVE: To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism. METHODS: Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells. RESULTS: 2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 µmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 µmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship. CONCLUSION: 2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.


Asunto(s)
Linfoma , Proteínas Proto-Oncogénicas c-bcl-2 , 2-Metoxiestradiol , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Regulación hacia Arriba , Proteína X Asociada a bcl-2
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 474-488, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812418

RESUMEN

OBJECTIVE: To investigate the effect and mechanism of a novel emodin derivative YX-18 on Burkitt lymphoma (BL) cells. METHODS: MTT assay was used to detect the effect of YX-18 on the proliferation of BL cell lines CA46 and Raji. Annexin V-PE/7-AAD double staining assay was used for detecting the effect of YX-18 on the apoptosis of CA46 and Raji cells. PI/RNase staining was used to test the effect of YX-18 on CA46 and Raji cell cycle. JC-1 method was used to measure the changes of mitochondrial membrane potential after YX-18 treatment, and DAPI staining was used to detect the morphology of apoptotic cells. Western blot was used to analyze the distribution changes of NF-κB pathway protein (P65, P-P65, IκB, P-IκB) in the cytoplasm and cell nucleus, and also the expression changes of cyclin-related protein P21, CDK2, P-CDK2, Cycling D1, Cycling E1, and the apoptosis-related protein Caspase-3, Caspase-8, Caspase-9 and the proliferation-related protein C-MYC, BCL-2 by YX-18. Real-time fluorescence-quantitative PCR was used to evaluate the effects of YX-18 on mRNA levels of C-MYC and Ki-67 genes in CA46 and Raji cells, and EBNA-1 and EBER genes of EBV in Raji (EBV+) cells. RESULTS: Novel Emodin derivative YX-18 could effectively inhibit the proliferation of BL cell lines CA46 and Raji, showing a time-dependent effect (24, 48 and 72 h: rCA46=0.89, 0.75, 0.75, rRaji=0.87, 0.73, 0.64). IC50 of CA46 cells and Raji cells treated with YX-18 for 24 h was 1.77±0.04 µmol/L and 1.97±0.22µmol/L, respectively. CA46 cells and Raji cells were treated with YX-18 at concentration of 2.0 and 4.0 µmol/L for 24 h. Compared with the control group, both strains of cells showed a very significant apoptosis at the concentration of 2.0 and 4.0 µmol/L (P<0.01), showing a concentration-dependent effect (rCA46=0.99, rRaji=0.92). Moreover, the cleavaged Caspase-3, 8 and 9 proteins were activated by YX-18 into verious degrees in both two cell lines. Both the two cell lines displayed by YX-18 cell cycle arrest at G0/G1 phase (P<0.01) after exposed to YX-18 for 24 hours at the concentration of 1.0, 2.0 µmol/L in CA46 cells and at 0.5 and 1 µmol/L in Raji cells, respectively. YX-18 decreased expression level of cyclin D1, cyclin E1, CDK2, p-cdk2 proteins and increased p21Waf1/Cip1 level in CA46 and Raji cells. YX-18 significantly declined mitochondrial membrane potential in both cells at the concentration of 2.0 and 4.0 µmol/l (P<0.01) with concentration-dependent manner (rCA46=-0.96, rRaji=-0.99). Western blot tests indicated that YX-18 down-regulated nucleus P65 and intracellular cytoplasm P65, P-IκB, P-P65 protein, and upregulated intracellular IκB level with dose-dependent manner. Meanwhile, the expression level of the cell proliferation-related molecules C-MYC and BCL-2 was decreased significantly. YX-18 suppressed mRNA levels of C-MYC and Ki-67 in both cell lines, and EBNA-1 in EBV-positive Raji cells in a concentration-dependent way. CONCLUSION: The novel emodin derivative YX-18 can significantly inhibit the proliferation of Burkitt lymphoma cells, and induce the cell apoptosis and cycle arrest. The inhibitory effect of YX-18 on the proliferation of Burkitt lymphoma cells may be related with the effect of Caspase apoptosis pathway, the proliferation and apoptosis-related molecules, such as C-MYC and Ki-67, and also to the inhibition of NF-κB pathway.


Asunto(s)
Linfoma de Burkitt , Emodina , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Emodina/farmacología , Humanos , FN-kappa B
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 494-499, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812420

RESUMEN

OBJECTIVE: To investigate the effect of long non-coding RNA-TUC338 on the proliferation and migration of lymphoma cells. METHODS: The expression of TUC338 in different lymphoma cells was detected by fluorescence quantitative PCR, cell proliferation by sulforhodamine B (SRB) assay, migration of lymphoma cells by transwell assay, and protein expression in PI3K/AKT signaling pathway by Western blot. RESULTS: The expression levels of TUC338 in lymphoma cells Daudi, U937, BC-3, and Raji significantly increased in comparison with human normal T lymphocytes H9 (t=13.277, 10.103, 16.200, and 26.687, P=0.002, 0.005, 0.001, and 0.000). Compared with NC-siRNA group, the number of cells crossing the chamber of TUC338-siRNA group was significantly reduced (t=30.508, P=0.000), the protein expression levels of p-PI3K and p-AKT significantly decreased (t=16.872 and 18.371, P=0.000 and 0.000), and OD530 absorbance values at 24 h, 48 h, and 72 h were significantly lower (P<0.05). CONCLUSION: The expression of TUC338 significantly increases in lymphoma cells, and silence of TUC338 effectively inhibits the activation of PI3K/AKT signaling pathway, thereby inhibiting the proliferation and migration of lymphoma cells, which has a potential application value in diagnosis and treatment of lymphoma.


Asunto(s)
ARN Largo no Codificante , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 515-519, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812423

RESUMEN

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 µmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H2DCFDA probe labeling. RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G2/M phase was increased to 28% and 40%, respectively. The cells in bortezomib group also showed a similar distribution after being treated. After treated with PX-12 and bortezomib, the cells in G1 phase were decreased significantly to 19% and 12% in S phase, but increased significantly to 68% in G2/M phase, which was significantly different from PX-12 group and bortezomib group (P<0.01). After culture for 72 hours, the apoptosis rate was 71.3% in the combination group, which was significantly higher than that in PX-12 group, bortezomib group, and control group (20.6%, 33.3%, 10.6%)(P<0.01). After culture for 24 hours, the intracellular ROS level in the combination group was 12015±430.2, which was higher than that in the PX-12 group, bortezomib group, and control group (6729±352.8, 2651±228.3, 1098±164.6, respectively) (P<0.01). CONCLUSION: PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.


Asunto(s)
Mieloma Múltiple , Apoptosis , Bortezomib/farmacología , Línea Celular Tumoral , Proliferación Celular , Humanos
11.
Artículo en Inglés | MEDLINE | ID: mdl-33822512

RESUMEN

The purpose of this study was to investigate the anti-inflammatory, antiproliferatiive, and proapoptotic molecular mechanisms of mangiferin (MGN) against mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA). Mammary cancer in rats was induced by single-dose subcutaneous injection of 0.5 ml DMBA (80 mg/kg in sesame oil) in the mammary gland. Increased tumor incidence and volume and other tumorigenic properties were observed. Further, we observed in these rats reduced antioxidant enzyme activity and elevated thiobarbituric acid reactive substance (TBARS) levels in plasma and tissues. DMBA-induced rats shows enhanced expression of the inflammatory markers NF-κBp65, COX-2, and iNOS and proliferation of PCNA and Cyclin D1, and overexpression of the antiapoptotic marker Bcl-2. Mangiferin (100 mg/kg body weight), administered orally once per day, significantly enhanced (p < 0.05) antioxidant levels and reduced TBARS levels. Moreover, MGN inhibited NF-κBp65 nucleus transcriptional activation, thereby suppressing inflammation and cell proliferation, and it increased proapoptotic proteins. Apoptosis was confirmed by TUNEL assay. In summary, MGN suppressed DMBA-induced mammary carcinogenesis through enhanced antioxidant levels, NF-κB inhibition, and positive regulation of apoptotic signals.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Xantonas/uso terapéutico , 9,10-Dimetil-1,2-benzantraceno , Animales , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinógenos , Proliferación Celular/efectos de los fármacos , Femenino , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Xantonas/farmacología
12.
J Environ Pathol Toxicol Oncol ; 40(2): 23-33, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33822514

RESUMEN

Aberrant expression of ß-tubulin-III (TUBB3) is known that related to aggressive tumor features and poor clinical outcomes. However, there is limited research about TUBB3 expression and its role in the outcomes and the progression of gallbladder cancer. We have measured TUBB3 level in gallbladder cancer samples and cell lines from 2012 to 2016, and tested the effects of TUBB3 in cancer cell growth, apoptosis and cell cycle arrest by using appropriate methods. The results revealed that TUBB3 was significantly over-expressed in gallbladder cancer samples and cell lines, and high TUBB3 level contributed to shorter overall survival in patients. The knockdown of TUBB3 with sh-TUBB3 inhibited the proliferation, migration and invasion of cancer cells. Meanwhile, it promotes apoptosis and changes the cell cycle distribution. Suppression of TUBB3 expression could increase p21 and cyclin B1 expression, and decrease cyclin D1. Xenograft mouse model also showed that low expression of TUBB3 reduced the growth of established gallbladder cancer xenograft in vivo. Furthermore, TUBB3 knockdown significantly decreased phosphorylation of Akt and mTOR in vitro and in vivo. TUBB3 can induce the development of gallbladder cancer by Akt/mTOR signal pathway and we point out a potential therapeutic target for gallbladder cancer treatment.


Asunto(s)
Neoplasias de la Vesícula Biliar/metabolismo , Tubulina (Proteína)/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Tubulina (Proteína)/genética
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 216-221, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33829694

RESUMEN

Objective: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. Methods: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. Results: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). Conclusion: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.


Asunto(s)
Acroleína , Células Epiteliales , Acroleína/farmacología , Proliferación Celular , Expresión Génica , Pulmón
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 439-444, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812412

RESUMEN

OBJECTIVE: To analyze the relationship of the expression of transcription factor MYB targeted regulation by miR-96 to cell invasion and apoptosis in pediatric acute myeloid leukemia (AML). METHODS: A total of 65 children with AML in The 928 Hospital of PLA Joint Logistics Support Forces from January 2017 to November 2019 were selected, including 35 cases diagnosed as primary AML and 30 cases as complete remission AML. Thirty children with immune thrombocytopenia were selected as control group. The clinical characteristics were analyzed and compared between the two groups. The levels of miR-96 and MYB in peripheral blood samples were detected by qRT-PCR and compared between the two groups. The miR-96 mimics and its negative control (NC), inhibitor-miR-96 and its NC transfected HL60 cells induced by liposome (Lipofectamine 2000), respectively, Then the expression levels of MYB were detected with Western blot and compared among four HL60 cell groups. The invasion ability of four HL60 cell groups were detected with Transwell assay. The cell proliferation ability of four HL60 cell groups were detected with MTT at 24 h, 48 h, and 72 h, respectively. The apoptosis rates of four HL60 cell groups were detected with flow cytometry. RESULTS: Compared with control group, the level of miR-96 in AML children were higher, but MYB lower (P<0.05). Compared with complete remission AML, the level of miR-96 in primary AML was higher, but MYB lower (P<0.05). Western blot analysis showed that, the expression level of MYB in the four HL60 cell groups was different (P<0.05), the lowest was in miR-96 mimics group, followed by miR-96 NC group and inhibitor-miR-96 NC group, and the highest in inhibitor-miR-96 group (P<0.05), while there was no difference between miR-96 NC group and inhibitor-miR-96 NC group (P>0.05). The promotion of over-expression level of miR-96 on the invasion ability of HL 60 cells was confirmed by Transwell assay. MTT assay showed that miR-96 could promote the proliferation of HL60 cells, inhibit the apoptosis of HL60 cells, and the effect was time-dependent manner (r=0.804). The inhibition of miR-96 on HL60 cells apoptosis was also confirmed with flow cytometry. CONCLUSION: MiR-96 has significant negative effect on invasion and apoptosis of AML cells by targeting regulation MYB, and it might be a potential novel strategy for pediatric AML treatment.


Asunto(s)
Leucemia Mieloide Aguda , MicroARNs , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Niño , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-myb
15.
Ecotoxicol Environ Saf ; 214: 112091, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33706141

RESUMEN

The occurrence of cadmium (Cd) in feed is a major problem in animal health and production. Studies have confirmed that Cd depresses egg production of laying hens, which is closely related to follicular atresia. This study aimed to assess the toxic impacts of Cd on the ovarian tissue, and to examine the mechanism of Cd-induced granulosa cell proliferation and apoptosis. Results from the nitric oxide (NO) and malondialdehyde (MDA) content, total superoxide dismutase (T-SOD), glutathione peroxide (GSH-Px), total nitric oxide synthase (T-NOS) and adenosine triphosphatase (ATPase) activities, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and hematoxylin-eosin (H & E) staining indicated that excess Cd induced oxidative stress, granulosa cell apoptosis and follicular atresia in the layer ovary. Low-dose Cd exposure (1 µM) induced the granulosa cell proliferation, upregulated the mRNA levels of RSK1 and RHEB, activated FoxO3a, AKT, ERK1/2, mTOR and p70S6K1 phosphorylation, and promoted cell cycle progression from phase G1 to S. However, high-dose Cd exposure (15 µM) induced reactive oxygen species (ROS) generation and cell apoptosis, upregulated the mRNA levels of the inflammatory factors, ASK1, JNK, p38 and TAK1, downregulated the expressions of RSK1 and RHEB genes, and inhibited the phosphorylation of ERK1/2, mTOR and p70S6K1 proteins, and the cell cycle progression. Rapamycin pre-treatment completely blocked the phosphorylation of mTOR and p70S6K1 proteins, and the cell cycle progression induced by 1 µM Cd, and accelerated 15 µM Cd-induced cell apoptosis and cell cycle arrest. The microRNA sequencing result showed that 15 µM Cd induced differential expression of microRNA genes, which may regulate AKT, ERK1/2 and mTOR signaling and cell cycle progression by regulating the activity of G proteins and cell cycle-related proteins. Conclusively, these results indicated that Cd can cause the ovarian damage and follicular atresia, and regulate cell cycle, cell proliferation or apoptosis of granulosa cells through MAPK, AKT/FoxO3a and mTOR pathways in laying hens.


Asunto(s)
Cadmio/toxicidad , Células de la Granulosa/efectos de los fármacos , Animales , Apoptosis , Ciclo Celular , Puntos de Control del Ciclo Celular , División Celular , Proliferación Celular , Pollos/metabolismo , Femenino , Atresia Folicular , Células de la Granulosa/metabolismo , Etiquetado Corte-Fin in Situ , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
16.
Nat Commun ; 12(1): 1670, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33723267

RESUMEN

Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-ß (TGFß) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFß signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFß can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-ß inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.


Asunto(s)
Cicatriz/terapia , Hidrogeles/farmacología , Iminas/química , Iminas/efectos de la radiación , Cicatrización de Heridas/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Cicatriz/patología , Modelos Animales de Enfermedad , Matriz Extracelular/efectos de los fármacos , Femenino , Fibroblastos , Masculino , Ratones , Conejos , Transducción de Señal , Piel/patología , Sus scrofa , Factor de Crecimiento Transformador beta/efectos de los fármacos
17.
Biol Res ; 54(1): 10, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33726823

RESUMEN

BACKGROUNDS: Parkinson's disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. METHODS: SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. RESULTS: MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. CONCLUSION: Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.


Asunto(s)
Apoptosis , Proliferación Celular , Glicoproteínas de Membrana/genética , MicroARNs/genética , Enfermedad de Parkinson/genética , ARN Largo no Codificante/genética , Células Cultivadas , Humanos
18.
Artículo en Chino | MEDLINE | ID: mdl-33781031

RESUMEN

Objective: To explore the chronic toxicity and its potential mechanism of multi-walled carbon nanotube (MWCNT) in human pleural mesothelial cells. Methods: A sustainable exposure of MeT-5A cells to MWCNT at 10 µg/cm(2) for one year was conducted in 2016. During the exposure, the cell images and cell proliferation was recorded every 4 weeks. The cell apoptosis, cell cycle, cell migration and cell invasion were compared between the control cells and the cells after MWCNT exposure. Finally, the gene expression was screened with Affymetrix clariom D assay, and some of the significantly differential expressed genes was verified by RT-PCR. Results: Compared with the control group, the proliferation ability of the cells in the 1-year exposed group was significantly increased, and the rate of proliferation was about 2-3 times as that in the Control Group (F=481.32, P<0.05) . MeT-5A cells all showed cell cycle arrest effect, which showed the increase of G1 phase and the decrease of s phase and G2 phase (F=14.94, P<0.05) . The apoptosis rate of cells in the treated group was significantly higher than that in the control group after 6 months (F=15.12, P<0.05) , but the early apoptosis rate and the total apoptosis rate of cells in the treated group were not significantly different from those in the control group after 1 year (F=3.97, P<0.05) . The cell migration and invasion were both promoted by MWCNT. Furthermore, the differentially expressed genes was screened, to find 2, 878 genes with more than 2 folds changes. To further verified, RT-PCR was conducted with PIK3R3、WNT2B、VANGL2、ANXA1, and their expression changes were consistent with above. Conclusion: MWCNT might have a carcinogenic potential to MeT-5A cells after the long term exposure.


Asunto(s)
Nanotubos de Carbono , Apoptosis , Carcinógenos , Ciclo Celular , Proliferación Celular , Humanos , Nanotubos de Carbono/toxicidad , Fosfatidilinositol 3-Quinasas
19.
Environ Monit Assess ; 193(4): 213, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33759015

RESUMEN

The study focused on developing a novel socio-economic drought index (SeDI) for monitoring the severity of drought in a dry basin ecosystem dominated by nomadic pastoralists. The study utilized the domestic water deficit index, bareness index, normalized difference vegetation index, and water accessibility index as the input variables. An ensembled stochastic framework that coupled the 3D Euclidean feature space algorithm, least-squares adjustment, and iteration was used to derive the new SeDI. This approach minimized the uncertainties propagated by the stochastic nature of the input variables that has been a major bottleneck exhibited by the existing models. The regression analyses between the simulated SeDI and the observed ground river discharge registered a correlation coefficient (r) of -0.84 and a p-value of 0.02, while the correlation between the Hull's score-derived SeDI and ground river discharge registered a correlation coefficient (r) of -0.75 and a p-value of 0.05. The assessment revealed that the newly derived SeDI was more sensitive to the river discharge than the Hull's score-derived SeDI. The SeDI's classification results for the period between 1986 and 2018 revealed that only January 2009 manifested a significant slight severity level covering about 12.4% of the basin. Additionally, the results indicated that the basin exhibited a moderate severity level ranging between 85 and 96%, a severe level ranging between 2.2 and 13.3%, and an extreme level ranging between 0.73 and 1.17%. The derived SeDI would serve as an early warning tool necessary for increasing the resilience to climate-related risks and offer support in reducing the loss of life and livelihood.


Asunto(s)
Sequías , Ríos , Proliferación Celular , Ecosistema , Monitoreo del Ambiente , Kenia , Factores Socioeconómicos
20.
Am J Vet Res ; 82(4): 318-325, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33764832

RESUMEN

OBJECTIVE: To investigate the effects of recombinant equine IL-1ß on function of equine endothelial colony-forming cells (ECFCs) in vitro. SAMPLE: ECFCs derived from peripheral blood samples of 3 healthy adult geldings. PROCEDURES: Function testing was performed to assess in vitro wound healing, tubule formation, cell adhesion, and uptake of 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) by cultured ECFCs. Cell proliferation was determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Effects on function test results of different concentrations and exposure times of recombinant equine IL-1ß were assessed. RESULTS: Challenge of cultured ECFCs with IL-1ß for 48 hours inhibited tubule formation. Continuous challenge (54 hours) with IL-1ß in the wound healing assay reduced gap closure. The IL-1ß exposure did not significantly affect ECFC adhesion, DiI-Ac-LDL uptake, or ECFC proliferation. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggested a role for IL-1ß in the inhibition of ECFC function in vitro. Functional changes in ECFCs following challenge with IL-1ß did not appear to be due to changes in cell proliferative capacity. These findings have implications for designing microenvironments for and optimizing therapeutic effects of ECFCs used to treat ischemic diseases in horses.


Asunto(s)
Células Endoteliales , Cicatrización de Heridas , Animales , Proliferación Celular , Células Cultivadas , Caballos , Interleucina-1beta , Masculino
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