Synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells
| Autor: | Jianfeng Xu, Wei Yin, Yanjiao Mao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Programmed cell death endocrine system diseases Mice Nude Apoptosis Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin Antineoplastic Combined Chemotherapy Protocols Autophagy Tumor Cells Cultured medicine Animals Humans Viability assay Propidium iodide Molecular Biology Cell Proliferation 030304 developmental biology Cisplatin Aldehydes 0303 health sciences Nasopharyngeal Carcinoma Drug Synergism Nasopharyngeal Neoplasms Cell Biology Xenograft Model Antitumor Assays chemistry Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Cancer research medicine.drug |
| Zdroj: | Biochemistry and Cell Biology. 99:322-329 |
| ISSN: | 1208-6002 0829-8211 |
| DOI: | 10.1139/bcb-2020-0283 |
| Popis: | This study explored the synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells by treating HNE-1 and cisplatin (diamminedichloroplatinum; DDP)-resistant HNE1/DDP nasopharyngeal cancer cell lines with DDP, autophagy inhibitors, or a combination of autophagy inhibitors and DDP. Cell viability was determined via MTT (colorimetric) and colony-forming assays, and the rate of apoptosis was determined using propidium iodide (PI) and annexin V double-staining. The expressions of proteins were determined by Western blotting. For our in-vivo studies, a murine xenograft model was established to evaluate the anti-tumor effects of the combination of autophagy inhibitor and DDP. The results showed that treatment with DDP increased the expressions of ATP-binding cassette sub-family B member 1 (ABCB1), ATP Binding Cassette Subfamily C Member 1 (ABCC1), and P-glycoprotein 1 (P-gp) in the HNE1/DDP cell lines. Treatment with chloroquine decreased the expression levels of ABCB1, ABCC1, and P-gp, and increased the formation of LC3-II and the expression levels of p62 in the HNE1/DDP cells. Additionally, the combination of autophagy inhibitors and DDP produced a synergistic effect on DDP-induced cell death and apoptosis. Furthermore, the combination of the autophagy inhibitor and DDP showed significant anti-tumor effects in the xenograft mouse model. In summary, autophagy inhibitors show synergistic anti-tumor effects with DDP in vitro against DDP-resistant nasopharyngeal cancer cells and in vivo in our xenograft murine model. |
| Databáze: | OpenAIRE |
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