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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
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