Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2021; 27(25): 3851-3862
Published online Jul 7, 2021. doi: 10.3748/wjg.v27.i25.3851
Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy
You-Han Miao, Li-Ping Mao, Xiao-Juan Cai, Xiao-Ying Mo, Qi-Qi Zhu, Fei-Tong Yang, Mei-Hua Wang
You-Han Miao, Li-Ping Mao, Xiao-Juan Cai, Xiao-Ying Mo, Qi-Qi Zhu, Fei-Tong Yang, Mei-Hua Wang, Department of Infectious Disease, Nantong Third People’s Hospital, Nantong 226006, Jiangsu Province, China
Author contributions: Miao YH and Mao LP contributed equally to this study; Miao YH and Mao LP performed the majority of experiments and analyzed the data; Cai XJ and Mo XY performed the molecular investigations; Zhu QQ, Yang FT, and Wang MH designed and coordinated the research; Miao YH wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Nantong Third People’s Hospital.
Institutional animal care and use committee statement: Animal care and method procedure were authorized by the Animal Ethics Committee of Nantong Third People’s Hospital.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mei-Hua Wang, PhD, Chief Physician, Department of Infectious Disease, Nantong Third People’s Hospital, No. 60 Qingnian Middle Road, Nantong 226006, Jiangsu Province, China. huatsbfyy3617@163.com
Received: December 27, 2020
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
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

To identify the role of ZnO-NP in the regulation of GC progression.

Research objectives

This study explored the effect of ZnO-NP on chemotherapy resistance during GC progression.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.