The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer

Wanjun Zhang; Junwei Niu; Yongcheng Ma; Xiawan Yang; Huixia Cao; Honggang Guo; Fengchang Bao; Ahmed Haw; Yuqing Chen; Kai Sun

doi:10.2147/OTT.S240721

The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer

Onco Targets Ther. 2020 May 6:13:3823-3837. doi: 10.2147/OTT.S240721. eCollection 2020.

Authors

Wanjun Zhang^#¹, Junwei Niu^#¹, Yongcheng Ma², Xiawan Yang¹, Huixia Cao³, Honggang Guo¹, Fengchang Bao¹, Ahmed Haw¹, Yuqing Chen¹, Kai Sun¹

Affiliations

¹ Department of Hematology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, People's Republic of China.
² Clinical Pharmacology Laboratory, Henan Provincial People's Hospital; Department of Pharmacy of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People's Republic of China.
³ Department of Nephrology, Henan Key Library for Kidney Disease and Immunology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: The aim of this study was to investigate the antitumor effect of chidamide in combination with bortezomib on gastric cancer cell lines.

Materials and methods: First, the sensitivity and IC₅₀ values of chidamide and bortezomib in several gastric cancer cell lines (MGC-803, BGC-823, SGC-7901, and MKN45) were measured using the CCK-8 assay. Then, the relatively insensitive gastric cancer cell lines (MGC-803 and BGC-823) were treated with low concentrations of chidamide alone, bortezomib alone, or chidamide and bortezomib combination to detect the effects on cell proliferation, apoptosis, migration, and invasion. Finally, the inhibitory effect of the combined chidamide and bortezomib treatment on MGC-803 cells was verified in vivo through tumor formation experiments in nude mice.

Results: Compared with low-dose chidamide or bortezomib alone, the low-dose drug combination significantly inhibited the proliferation, migration, and invasion of MGC-803 and BGC-823 cells and induced apoptosis of the cells. The effects of the low-dose chidamide and bortezomib combination reduced the growth on gastric cancer in vivo were investigated by using a subcutaneous tumor mouse model.

Conclusion: Our results suggest that the combination of chidamide and bortezomib can significantly reduce the proliferation, invasion, and migration of MGC-803 and BGC-823 cells, providing a framework for the clinical evaluation of combined therapies for gastric cancers.

Keywords: bortezomib; combination drug therapy; gastric cancer; chidamide.

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81971508, 81471589, 81273259); the Health Bureau of Henan Province (No. 201201005) and the Foundation and Frontier Research Grant of Henan Provincial Science and Technology Bureau (No. 142300410078 and No. 162102310293).