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
Abstract
BACKGROUND

Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related 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.

Keywords: Gastric cancer, Progression, Chemoresistance, Zinc oxide nanoparticle, Autophagy, MTT assays

Core Tip: We show that zinc oxide nanoparticle (ZnO-NP) reduces the chemoresistance of gastric cancer (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.