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

Authors Li L, Zhang S, Xie D, Chen H, Zheng X, Pan D

Received 3 May 2018

Accepted for publication 24 July 2018

Published 20 September 2018 Volume 2018:11 Pages 6111—6118

DOI https://doi.org/10.2147/OTT.S172957

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai


Liangqing Li, Shengwei Zhang, Diya Xie, Hui Chen, Xuelan Zheng, Dun Pan

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China

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.

Keywords: NVP-BEZ235, fluorouracil, gastric cancer, chemotherapy, P13K, mTOR

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