Isovitexin potentiated the antitumor activity of cisplatin by inhibiting the glucose metabolism of lung cancer cells and reduced cisplatin-induced immunotoxicity in mice
| Autor: | Jia-Qi He, Cai-Hua Sun, Chen-Huan Yu, Huan-Huan Zhang, Zhen Wang, Ping Huang, Rui-Lin Chen, Wen-Ying Yu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Thyroid Hormones Lung Neoplasms endocrine system diseases Immunology Cell Down-Regulation Mice Nude Antineoplastic Agents PKM2 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Splenocyte Animals Humans Immunology and Allergy Cytotoxic T cell Lactic Acid Apigenin Lung cancer Cell Proliferation Pharmacology Cisplatin Cell growth Chemistry Membrane Proteins Drug Synergism medicine.disease Killer Cells Natural Glucose 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Cancer research Cytokines Carrier Proteins T-Lymphocytes Cytotoxic medicine.drug |
| Zdroj: | International Immunopharmacology. 94:107357 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2020.107357 |
| Popis: | The increased resistance and toxicity have become the main causes of chemotherapy failure for treating lung cancer. The combination of chemotherapeutic drugs with other agents has been recognized as a promising strategy to overcome these difficulties. Isovitexin (IVT) is a well-known flavone C-glycoside found in many plants and has attracted wide attention due to its obvious antitumor and antioxidant effects. In this study, we investigated the synergistic effects of IVX and cisplatin (DDP) in non-small cell lung cancer (NSCLC) A549 and H1975 cells. The results showed that the combined treatment with IVT and DDP markedly inhibited proliferation and induced apoptosis of the two NSCLC cells. Using a mouse model of A549 xenograft, IVT potentiated the inhibition of DDP on tumor growth, but reduced DDP-induced hepatotoxicity and nephrotoxicity in mice. Remarkedly, IVT promoted lipopolysaccharide (LPS)- and lectin- stimulated splenocyte proliferation, and enhance cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activities as well as the production of IL-2 and TNF-α. Furthermore, IVT significantly reduced glucose uptake, lactate production, and ATP production, and downregulated the protein expressions of pyruvate kinase M2 (PKM2)-mediated pathway in both A549 and H1975 cells. After the over-expression of PKM2 in the NSCLC cells, the synergistic antitumor effect of IVT and DDP was markedly weakened. Therefore, IVT not only inhibited cell proliferation and glucose metabolism via downregulating the expression of PKM2 to enhance the antitumor activity of DDP against lung cancer cells, and improved DDP-induced immunotoxicity in mice. It also presented a novel strategy to enhance the anti-tumor effect of platinum-based chemotherapy against NSCLC. |
| Databáze: | OpenAIRE |
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