Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy.

Abstract

PURPOSE:

NVP-BEZ235 is a recently developed dual inhibitor of PI3K and mTOR and shows good inhibitory effects on several types of tumors. However, the efficacy of NVP-BEZ235 on gastric cancer therapy remains unclear. This study aimed to investigate the potential of NVP-BEZ235 as a new agent to enhance chemotherapy for gastric cancer.

METHODS:

Human gastric cancer MKN-45 cells or nude mice xenografted with MKN-45 cells were treated by NVP-BEZ235 and fluorouracil (5-FU) alone or in combination. The proliferation, invasion, apoptosis, and chemoresistance of gastric cancer cells were examined in vivo and in vitro.

RESULTS:

In vitro, combined treatment with NVP-BEZ235 and 5-FU showed synergistic inhibitory effects on proliferation, migration, and invasion and synergistic stimulating effects on apoptosis of MKN-45 cells. In vivo, NVP-BEZ235 and 5-FU synergistically inhibited the growth and induced apoptosis of MKN-45 xenografts. Mechanistically, NVP-BEZ235 inhibited PI3K/Akt/mTOR signaling; decreased the levels of Bcl-2, MMP9, and VEGF; but increased the levels of Bax and cleaved caspase-3 in MKN-45 xenografts.

CONCLUSION:

NVP-BEZ235 enhances the antitumor efficacy of 5-FU. Therefore, NVP-BEZ235 is a promising agent to enhance chemotherapy for gastric cancer.

• Authors: Liangqing Li, Shengwei Zhang, Diya Xie, Hui Chen, Xuelan Zheng, Dun Pan
• Journal: OncoTargets and therapy (Onco Targets Ther) Vol. 11 Pg. 6111-6118 ( 2018) ISSN: 1178-6930 [Print] New Zealand
• PMID: 30275715 (Publication Type: Journal Article)