NVP-BEZ235, a dual PI3K-mTOR inhibitor, suppresses the growth of FaDu hypopharyngeal squamous cell carcinoma and has a synergistic effect with Cisplatin

Cheng Ming Hsu, Pai Mei Lin, Yao Te Tsai, Ming Shao Tsai, Chun Han Tseng, Sheng Fung Lin*, Ming Yu Yang

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

29 引文 斯高帕斯(Scopus)

摘要

NVP-BEZ235 is a dual phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor. A dual approach targeting more than one downstream effector is a promising strategy for treating cancers. The aim of this study was to evaluate the effect of NVP-BEZ235 in treating FaDu hypopharyngeal squamous cell carcinoma (HSCC), either alone or in combination with cisplatin. We found mTOR expression was higher in patients with HSCC. In the in vitro study, treatment with NVP-BEZ235 alone attenuated cell proliferation and suppressed p-p70S6K and p-4E-BP1 expression in FaDu cells. When NVP-BEZ235 was combined with Cisplatin, apoptosis was induced more effectively than with either drug alone. In mice with a FaDu xenograft, cotreatment with NVP-BEZ235 and Cisplatin engendered synergistic effects and produced a greater antitumor response than did treatment with either drug alone. Resected tumor samples also showed decreased p-p70S6K expression. Collectively, these data demonstrate that NVP-BEZ235 inhibits HSCC growth through phospho-p70S6K suppression and has a synergistic effect with Cisplatin in treating HSCC. The data also provide a strategy for more effective HSCC treatment.

原文英語
文章編號57
期刊Cell Death Discovery
4
發行號1
DOIs
出版狀態已出版 - 01 12 2018

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© 2018, The Author(s).

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