The Dual PI3K/mTOR Inhibitor BEZ235 Is Effective in Lung Cancer Cell Lines (original) (raw)

2011, Anticancer Research

Background: BEZ235 is a dual phosphatidylinositol 3-kinase (PI 3 K)/mammalian target of rapamycin (mTOR) inhibitor that is orally available and that has been shown to be effective in several malignancies in vitro. Recently, BEZ235 entered clinical trials for solid tumors. We aimed at investigating if BEZ235 is effective in lung cancer cell lines. Materials and Methods: The human lung cancer cell lines EPLC, HCC and H1339 were analysed by fluorescence in situ hybridization, gene sequencing and Western blot analysis. Cells were exposed to BEZ235 and/or cisplatin and the survival fraction was quantified. Results: In all cell lines, BEZ235 reduced pAkt and pS6 expression indicating interference with the epidermal growth factor (EGF) pathway. Furthermore, BEZ235 inhibited tumor cell growth and added to the effects of cisplatin. This was independent of EGFR amplification and EGFR, KRAS, PI3K and AKT mutation. Conclusion: The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines and a promising compound to be tested in clinical phase I studies.

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