Published online Jul 7, 2021. doi: 10.3748/wjg.v27.i25.3851
Peer-review started: December 27, 2020
First decision: January 23, 2021
Revised: January 27, 2021
Accepted: March 15, 2021
Article in press: March 15, 2021
Published online: July 7, 2021
Processing time: 190 Days and 12.1 Hours
Gastric cancer (GC) is a common cancer and results in a high rate of tumor-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line treatment of GC, but chemoresistance remains a severe clinical problem. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but its role in GC development is still unclear.
To identify the role of ZnO-NP in the regulation of GC progression.
This study explored the effect of ZnO-NP on chemotherapy resistance during GC progression.
ZnO-NP was synthesized, and the effect and underlying mechanism on the malignant progression and chemotherapy resistance of GC cells were assessed by tumorigenicity in nude mice and evaluated by Western blotting, flow cytometry analysis, wound healing assays, transwell assays, colony formation assays, and MTT assays in GC cells and DDP-resistant GC cells.
ZnO-NP inhibited proliferation, migration, and invasion and induced apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the IC50 value of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in the chemotherapy-resistant GC cells, as demonstrated by elevated LC3II/LC3I and Beclin-1 expression and repressed p62 expression in the SGC7901/ DDP compared with that in SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells, and treatment with DDP induced autophagy in the cells, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of chemoresistant GC cells in vivo.
ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings provide innovative insights into the scenario in which ZnO-NP mediates chemotherapy resistance in 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 to be clarified in future investigations.