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  • Title: Synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells.
    Author: Yin W, Xu J, Mao Y.
    Journal: Biochem Cell Biol; 2021 Jun; 99(3):322-329. PubMed ID: 34038188.
    Abstract:
    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.
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