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

Cell Death Discovery
Cheng-Ming HsuMing-Yu Yang

Abstract

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.

References

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Citations

May 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cheng-Chan YuSheng-Chun Chiu
Oct 12, 2018·International Journal of Molecular Sciences·Gan QiaoXiukun Lin
Feb 28, 2019·Cancer Research·Mengqiu SongMee-Hyun Lee
Nov 2, 2019·Molecular Cancer Therapeutics·Areumnuri KimJae Kyung Myung
Apr 16, 2021·Expert Review of Anticancer Therapy·Said M AfifyMasaharu Seno
Jun 12, 2021·ChemMedChem·Chiara BorsariMatthias P Wymann
Aug 28, 2021·Journal of Cellular Physiology·Prashant KumarAmit Mishra

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Methods Mentioned

BETA
flow cytometry
xenograft
xenografts
PCR
electrophoresis

Software Mentioned

SPSS

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