OncoTargets and Therapy (May 2020)
The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer
Abstract
Wanjun Zhang,1,* Junwei Niu,1,* Yongcheng Ma,2 Xiawan Yang,1 Huixia Cao,3 Honggang Guo,1 Fengchang Bao,1 Ahmed Haw,1 Yuqing Chen,1 Kai Sun1 1Department of Hematology, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 2Clinical 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; 3Department 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*These authors contributed equally to this workCorrespondence: Kai Sun; Yuqing ChenDepartment of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People’s Republic of ChinaTel/Fax +86 371 65580798Email [email protected]; [email protected]: 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: chidamide, bortezomib, combination drug therapy, gastric cancer
