Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy

摘要

BACKGROUND Gastric cancer(GC)is a common malignancy that results in a high rate of cancerrelated mortality.Cisplatin(DDP)-based chemotherapy is the first-line clinical treatment for GC therapy,but chemotherapy resistance remains a severe clinical challenge.Zinc oxide nanoparticle(ZnO-NP)has been identified as a promising anti-cancer agent,but the function of ZnO-NP in GC development is still unclear.AIM To explore the effect of ZnO-NP on chemotherapy resistance during GC progression.METHODS ZnO-NP was synthesized,and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays,colony formation assays,transwell assays,wound healing assays,flow cytometry,and Western blot analysis in GC cells and DDP-resistant GC cells,and by tumorigenicity analyses in nude mice.RESULTS Our data revealed that ZnO-NP was able to inhibit proliferation,migration,and invasion and induce apoptosis of GC cells.Meanwhile,ZnO-NP significantly reduced the half maximal inhibitory concentration(IC50)of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines.Autophagy was increased in DDP-resistant GC cells,as demonstrated by elevated light chain 3-like protein 2(LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells.Mechanically,ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy,which was reversed by ZnO-NP.Functionally,ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo.CONCLUSION We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy.Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC.ZnO-NP may serve as a potential therapeutic candidate for GC treatment.The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.