Synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells.
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.
['Yin|Wei|W|', 'Xu|Jianfeng|J|', 'Mao|Yanjiao|Y|']
D000447:Aldehydes D000818:Animals D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D001343:Autophagy D049109:Cell Proliferation D002945:Cisplatin D019008:Drug Resistance, Neoplasm D004357:Drug Synergism D006801:Humans D008297:Male D051379:Mice D008819:Mice, Nude D000077274:Nasopharyngeal Carcinoma D009303:Nasopharyngeal Neoplasms D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
autophagie autophagie cisplatin cisplatin nasopharyngeal cancer HNE1/DDP chloroquine autophagy cancer du nasopharynx cisplatine