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BACKGROUND: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors. AIM: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it. METHODS: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed. RESULTS: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor. CONCLUSION: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered.
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Breast cancer is one of the most common female malignant tumors, with triple-negative breast cancer (TNBC) being the most specific, highly invasive, metastatic and associated with a poor prognosis. Our previous study showed that the natural product ganoderic acid A (GAA) has a certain affinity for MDM2. In this study, two series of novel GAA PROTACs C1-C10 and V1-V10 were designed and synthesized for the treatment of breast cancer. The antitumor activity of these compounds was evaluated against four human tumor cell lines (MCF-7, MDA-MB-231, SJSA-1, and HepG2). Among them, V9 and V10 showed stronger anti-proliferative effects against breast cancer cells, and V10 showed the best selectivity in MDA-MB-231 cells (TNBC), which was 5-fold higher than that of the lead compound GAA. Preliminary structure-activity analysis revealed that V-series GAA PROTACs had better effects than C-series, and the introduction of 2O-4O PEG linkers could significantly improve the antitumor activity. Molecular docking, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and Western blot researches showed that both V9 and V10 could bind with MDM2, and degrade the protein through the ubiquitin-proteasome system. Molecular dynamics simulation (MD) revealed that V10 is a bifunctional molecule that can bind to von Hippel-Lindau (VHL) at one end and target MDM2 at the other. In addition, V10 promoted the upregulation of p21 in p53-mutant MDA-MB-231 cells, and induced apoptosis via down-regulation of the bcl-2/bax ratio and the expression of cyclin B1. Finally, in vivo experiments showed that, V10 also exhibited good tumor inhibitory activity in xenografted TNBC zebrafish models, with an inhibition rate of 27.2% at 50 µg/mL. In conclusion, our results suggested that V10 has anti-tumor effects on p53-mutant breast cancer in vitro and in vivo, and may be used as a novel lead compound for the future development of TNBC.
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Ácidos Heptanoicos , Lanosterol/análogos & derivados , Proteínas Proto-Oncogênicas c-mdm2 , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/metabolismo , Simulação de Acoplamento Molecular , Peixe-Zebra/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , ApoptoseRESUMO
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.
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A series of novel NBP-TMP hybrids with neuroprotective effects were designed and synthesized for the treatment of ischemic stroke. The anti-cerebral ischemic activity of these compounds was screened by evaluating their neuroprotective effects on the oxygen glucose deprivation/reperfusion (OGD/R)-induced SH-SY5Y cell injury model in vitro. Nine compounds 7e, 7h-7i, 7k, 7m-7p and 7r showed better activities on cell viability and LDH levels compared to NBP at the concentration of 6.25 µM. Among them, compound 7m showed the best potency with a percentage of protection 90.2 % compared to NBP (69.2 %) and other compounds. Preliminary structure-activity analysis revealed that the introduction of iodine and N-methylpiperazine groups could significantly improve the neuroprotective effect. Further mechanism research showed that compound 7m could reduce the damage to neuronal mitochondria caused by OGD/R by reducing ROS and increasing mitochondrial membrane potential (MMP), and reduce the apoptosis and necrosis of neurons to play a neuroprotective role. In addition, 7m could regulate the levels of mitochondrial apoptosis pathway-related proteins Bcl-2, Bax, and caspase 3. Finally, in vivo experiments showed that the compound 7m significantly inhibited ischemia-reperfusion injury and cerebral blood flow in rats, and showed a more significant neuroprotective effect than the positive drug NBP at a dose concentration of 20 mg/kg. In conclusion, our results suggest that 7m may be used as a novel lead compound for the future development of anti-cerebral ischemic agents.
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AVC Isquêmico , Neuroblastoma , Fármacos Neuroprotetores , Ratos , Humanos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Apoptose , Oxigênio/metabolismo , Glucose/metabolismoRESUMO
A series of ursodeoxycholic acid (UDCA)-cinnamic acid hybrids were designed and synthesized. The anti-inflammatory activity of these derivatives was screened through evaluating their inhibitory effects of LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was concluded. Among them, 2m showed the best inhibitory activity against NO (IC50 = 7.70 µM) with no significant toxicity. Further study revealed that 2m significantly decreased the levels of TNF-α, IL-1ß, IL-6 and PGE2, down-regulated the expression of iNOS and COX-2. Preliminary mechanism study indicated that the anti-inflammatory activity of 2m was related to the inhibition of the Akt/NF-κB and MAPK signaling pathway. Furthermore, 2m reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo. In brief, our findings indicated that 2m might serve as a new lead compound for further development of anti-inflammatory agents.
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NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Ácido Ursodesoxicólico/farmacologia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Transdução de SinaisRESUMO
The mechanisms of action of natural products and the identification of their targets have long been a research hotspot. Ganoderic acid A (GAA) is the earliest and most abundant triterpenoids discovered in Ganoderma lucidum. The multi-therapeutic potential of GAA, in particular its anti-tumor activity, has been extensively studied. However, the unknown targets and associated pathways of GAA, together with its low activity, limit in-depth research compared to other small molecule anti-cancer drugs. In this study, GAA was modified at the carboxyl group to synthesize a series of amide compounds, and the in vitro anti-tumor activities of the derivatives were investigated. Finally, compound A2 was selected to study its mechanism of action because of its high activity in three different types of tumor cell lines and low toxicity to normal cells. The results showed that A2 could induce apoptosis by regulating the p53 signaling pathway and may be involved in inhibiting the interaction of MDM2 and p53 by binding to MDM2 (KD = 1.68 µM). This study provides some inspiration for the research into the anti-tumor targets and mechanisms of GAA and its derivatives, as well as for the discovery of active candidates based on this series.
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Antineoplásicos , Triterpenos , Proteína Supressora de Tumor p53 , Triterpenos/química , Antineoplásicos/farmacologia , ApoptoseRESUMO
Matrine is a clinically used adjuvant anticancer drug, yet its mild potency limited its application. To improve the anticancer activity of matrine, a total of 31 indole-matrine hybrids were constructed in four rounds of SAR-guided iterative structural optimization process. All of the synthesized compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines (Hela, MCF-7, SGC-7901, HepG2) and two normal cell lines (GES-1, LO2). The most active hybrid 8g exhibited the anticancer IC50 values of 0.9 to 1.2 µM, which was 3-magnitude of orders more potent than matrine. 8g also showed better selectivity towards cancer cells with the selectivity index value raised from 1.5 to 6.2. Mechanistic studies demonstrated a mitochondrial distribution for 8g by intracellular click chemistry approaches, which led to the discovery that 8g strongly induced mitochondrial stress, as evidenced by impaired energy metabolism, depolarized mitochondrial membrane potential, overload of mitochondrial calcium and escalated ROS production. 8g-induced mitochondrial stress further led to the release of cytochrome c and subsequent activation of caspase 3, which significantly promoted cellular death and inhibited colony formation.
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Antineoplásicos , Caspases , Humanos , Caspases/metabolismo , Citocromos c/metabolismo , Matrinas , Caspase 3/metabolismo , Linhagem Celular Tumoral , Apoptose , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células , Potencial da Membrana MitocondrialRESUMO
A series of novel aloe-emodin-coumarin hybrids were designed and synthesized. The antitumor activity of these derivatives was evaluated against five human tumor cell lines (A549, SGC-7901, HepG2, MCF-7 and HCT-8). Some of the synthesized compounds exhibited moderate to good activity against one or more cell lines. Particularly, compound 5d exhibited more potent antiproliferative activity than the reference drug etoposide against all tested tumor cell lines, indicating that it had a broad spectrum of antitumor activity and that it may provide a promising lead compound for further development as an antitumor agent by structural modification. Furthermore, the structure-activity relationship study of the synthesized compounds was also performed.
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Aloe , Antineoplásicos , Emodina , Antraquinonas , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Cumarínicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Emodina/farmacologia , Etoposídeo/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The development of new technologies for the separation, selection, and isolation of microparticles such as rare target cells, circulating tumor cells, cancer stem cells, and immune cells has become increasingly important in the last few years. Microparticle separation technologies are usually applied to the analysis of disease-associated cells, but these procedures often face a cell separation problem that is often insufficient for single specific cell analyses. To overcome these limitations, a highly accurate size-based microparticle separation technique, herein called "rotating magnetic chromatography", is proposed in this work. Magnetic nanoparticles, placed in a microfluidic separation channel, are forced to move in well-defined trajectories by an external magnetic field, colliding with microparticles that are in this way separated on the basis of their dimensions with high accuracy and reproducibility. The method was optimized by using fluorescein isothiocyanate-modified polystyrene particles (chosen as a reference standard) and then applied to the analysis of cancer cells like Hep-3B and SK-Hep-1, allowing their fast and high-resolution chromatographic separation as a function of their dimensions. Due to its unmatched sub-micrometer cell separation capabilities, RMC can be considered a break-through technique that can unlock new perspectives in different scientific fields, that is, in medical oncology.
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Cromatografia , Magnetismo , Separação Celular , Fenômenos Magnéticos , Poliestirenos/química , Reprodutibilidade dos TestesRESUMO
To discover novel anti-inflammatory agents, a series of nitrogen-containing derivatives of aloe-emodin were designed and synthesized. The anti-inflammatory activities of all synthesized derivatives were screened by evaluating their inhibitory effects on LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was determined. Among them, 2i exhibited the best nitric oxide inhibitory activity (IC50 = 3.15 µM), with no obvious toxicity. Further evaluation of the inhibitory effect of 2i on inflammatory cytokines showed that 2i significantly reduced the levels of TNF-α, IL-1ß, IL-6 and PGE2. In addition, 2i markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of 2i might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that 2i might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.
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Aloe , Emodina , Aloe/metabolismo , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Natural products are an important source of drug lead compounds, and natural products with significant biological activity are constantly being discovered and used in clinical practice. At present, natural products play an important role in the targeted therapy of cancer, cardiovascular and cerebrovascular diseases, nervous system diseases, and autoimmune diseases. Meanwhile, in recent years, the rise of protein-targeted degradation technologies, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, has provided a new solution for drug resistance caused by clinical molecular-targeting drugs. It is noteworthy that natural products and their derivatives, as important components of PROTACs and molecular glues, play an important role in the development of protein-targeting drugs. Hence, this review summarized the protein-targeted degradation agents based on natural products, such as PROTACs and molecular glues. More natural products with the potential to be used in the development of PROTACs and molecular glues as targeted protein degradation agents are still being investigated.
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Three new caffeoyl derivatives (1-3), together with two known ones (4-5), were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 4 was obtained and its NMR data were given for the first time. All isolates were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and pro-inflammatory cytokines release in RAW 264.7 cells. Compounds 2-5 showed mild inhibitory activities with IC50 values ranging from 64.78 to 87.21 µM, and 3-4 could inhibit LPS-induced tumor necrosis factor-α (TNF-α) production.
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Asteraceae , Lipopolissacarídeos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Asteraceae/química , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico , Células RAW 264.7RESUMO
Autotaxin (ATX) is the only enzyme of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP2) family with lysophospholipase D (lysoPLD) activity, which is mainly responsible for the hydrolysis of extracellular lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA can induce various responses, such as cell proliferation, migration, and cytokine production, through six G protein-coupled receptors (LPA1-6). This signaling pathway is associated with metabolic and inflammatory disorder, and inhibiting this pathway has a positive effect on the treatment of related diseases, while ATX, as an important role in the production of LPA, has been shown to be associated with the occurrence and metastasis of tumors, fibrosis and cardiovascular diseases. From mimics of ATX natural lipid substrates to the rational design of small molecule inhibitors, ATX inhibitors have made rapid progress in structural diversity and design over the past 20 years, and three drugs, GLPG1690, BBT-877, and BLD-0409, have entered clinical trials. In this paper, we will review the structure of ATX inhibitors from the perspective of the transformation of design ideas, discuss the advantages and disadvantages of each inhibitor type, and put forward prospects for the development of ATX inhibitors in the future.
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Cholangiocarcinoma (CCA) is a malignant tumor with poor prognosis and high recurrence rate. There is no standard treatment for advanced CCA beyond first-line chemotherapy, which provides only limited benefits. In this study, we report a case of a postoperative recurrence ECC patient harboring a breast cancer 2 (BRCA2)-inactivating rearrangement mutation that had an obvious reaction to olaparib therapy. The patient was a 68-year-old man with postoperative recurrence of extrahepatic CCA (ECC) who declined systemic chemotherapy. In August 2015, abdominal computed tomography (CT) of the patient revealed intrahepatic bile duct dilatation, obstruction at the hepatic hilar region proximal to the common hepatic duct, and splenomegaly, and radical surgical resection was performed. Postoperative histopathology diagnosis was ECC without metastases. In February 2017, abdominal CT revealed local recurrence, and the patient refused chemotherapy. BRCA2 rearrangement were detected by next-generation sequencing. Oral administration of olaparib was initiated. The patient achieved stable disease 1 month later, progression-free survival for >10 months without any significant adverse reactions, and an overall survival (OS) of 27 months. This is the first report demonstrating the clinical benefits of olaparib in a BRCA2 rearrangement-harboring patient with ECC. This observation would help determine the best treatment option for advanced ECC patients.
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A reciprocating magnetic-field-assisted on-line solid-phase extraction (RMF-SPE) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for continuous enrichment of trace chemicals in water samples. Under the assist of the reciprocating magnetic field, carboxyl-modified magnetic nanoparticles (CMNPs) were applied to prepare microcolumn with even dispersion by periodical motion, instead of traditional compaction as extraction sorbents. When water sample passed through the extraction region, dynamic sorbents generates an advantage of countless contacts between sorbents and targets without blocking for high efficient extraction. In this study, the on-line RMF-SPE method was established and evaluated by determination of tetracyclines (TCs) from water samples as analysis models, including oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline, and doxycycline. Experimental conditions have been investigated such as flow rate, reciprocating speed, elution time, and so on. The method showed high relative recovery (95.4-111.1%) and good repeatability with RSD from 2.9 to 11.8% for the 200 mL water sample. The linearity range, limits of detection (LODs), and limits of quantification (LOQs) were 0.5-200 µg L-1 (chlortetracycline) and 0.1-200 µg L-1 (other TCs), 12.0-74.1 ng L-1, and 40.1-247 ng L-1, respectively. More importantly, the high enrichment factors in a range of 204 (chlortetracycline) to 276 (demeclocycline) indicate that a small amount of dynamic sorbents (only 10 mg) give full play to extraction attributing to the reciprocating movement, especially for trace analysis and continuous extraction, which is significant for water samples from sea, river and domestic waste.
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Tetraciclinas , Água , Cromatografia Líquida , Campos Magnéticos , Extração em Fase Sólida , Espectrometria de Massas em TandemRESUMO
Benzene derivatives (BDs) constitute a class of environmental pollutants whose exposure poses a grave risk to human health. These compounds rapidly diffuse from the atmosphere to the marine ecosystem: for this reason, their monitoring in seawater is every day more compelling. In this work, nanoconfined liquid phase nanoextraction (NLPNE), a versatile extraction technique recently described, has been for the first time applied to the gas chromatographic mass spectrometry (GC/MS) analysis of BDs in seawater. Ex-situ and in-situ NLPNE procedures have been developed and optimized in terms of extraction capabilities, analysis time, precision, and accuracy. Compared to the traditional extraction procedures, based on solid-phase microextraction (SPME) and liquid-liquid extraction (LLE), the proposed NLPNE methods allowed a rapid on-site analysis of benzene compounds with low solvent consumption, higher enrichment factors, and improved automation grade. Determination coefficients ranging from 0.9929 to 0.9997 were obtained for all BDs in the range 0.10-500 ng mL-1 and 5.00-500 ng mL-1, for ex-situ and in-situ NLPNE, respectively. Ex-situ and in-situ limits of detection ranged from 0.2 to 7.6 ng mL-1 and 0.04-1.00 ng mL-1. Our results suggest that NLPNE coupled to GC-MS can be considered a powerful technique for high-throughput analyses of trace compounds in environmental, food and biological samples.
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Derivados de Benzeno , Poluentes Químicos da Água , Derivados de Benzeno/análise , Ecossistema , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Água do Mar , Poluentes Químicos da Água/análiseRESUMO
miRNA-21 is a single-stranded non-coding RNA that is highly expressed in a variety of tumor cells. It participates in tumor cell proliferation, metabolism, metastasis, and drug resistance. Here, we tested the potential mechanism of miRNA-21 in cisplatin-resistant non-small cell lung cancer A549/DDP (human lung adenocarcinoma drug-resistant cell line) cells. A549 and A549/DDP RNAs were sequenced to show that miRNA-21 was highly expressed in the latter, and this was verified by qRT-PCR. In addition, we found that miRNA-21 combined with cisplatin can significantly inhibit glycolysis and glycolysis rate-limiting enzyme protein expression in A549/DDP cells. We also found that miRNA-21 combined with cisplatin can promote A549/DDP cell death. Further investigations showed that miRNA-21 combined with cisplatin caused excessive inactivation of the pI3K/AKT/mTOR/HIF-1α signaling pathway in cisplatin-resistant A549/DDP cells. Hence, reduction of the expression of miRNA-21 in combination with cisplatin chemotherapy may effectively improve the therapeutic effect on patients with non-small cell lung cancer, and this may provide a theoretical basis for the treatment of this disease.
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Two new phenolic acids, ethyl 3,3',4,4'-tetrahydroxy-δ-truxinate (1), 3-O-p-coumaroyl-4-O-caffeoyl quinic acid methyl ester (2), together with three known compounds (3-5) were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 3 was obtained and given its NMR data for the first time. All isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, and 1, 4 and 5 showed a moderate inhibition with IC50 values ranging from 11.85 to 20.62 µM.
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Asteraceae , Animais , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos , Macrófagos , Camundongos , Óxido Nítrico , Células RAW 264.7RESUMO
Tumor cells, especially drug-resistant cells, predominately support growth by glycolysis even under the condition of adequate oxygen, which is known as the Warburg effect. Glucose metabolism reprogramming is one of the main factors causing tumor resistance. Previous studies on Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of tumors in combination with chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with cisplatin on cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that cisplatin-resistant A549/DDP cells exhibited increased glucose consumption, lactate production, and expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M1/2 (PKM1/2), pyruvate kinase M2 (PKM2), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA), compared with cisplatin-sensitive A549 cells. SMI combined with cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic enzymes, such as HK2, PKM1/2, GLUT1, and pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p-Akt, p-mTOR, and c-Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of cisplatin via glucose metabolism reprogramming. Therefore, the combination of SMI and cisplatin may be a potential therapeutic strategy to treat cisplatin-resistant nonsmall cell lung cancer.