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.
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 humanlung 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.
Authors: Rui Li; Chunyong Ding; Jun Zhang; Maohua Xie; Dongkyoo Park; Ye Ding; Guo Chen; Guojing Zhang; Melissa Gilbert-Ross; Wei Zhou; Adam I Marcus; Shi-Yong Sun; Zhuo G Chen; Gabriel L Sica; Suresh S Ramalingam; Andrew T Magis; Haian Fu; Fadlo R Khuri; Walter J Curran; Taofeek K Owonikoko; Dong M Shin; Jia Zhou; Xingming Deng Journal: Cancer Res Date: 2017-04-05 Impact factor: 12.701
Authors: Jatin Roper; Michael P Richardson; Wei Vivian Wang; Larissa Georgeon Richard; Wei Chen; Erin M Coffee; Mark J Sinnamon; Lydia Lee; Peng-Chieh Chen; Roderick T Bronson; Eric S Martin; Kenneth E Hung Journal: PLoS One Date: 2011-09-26 Impact factor: 3.240
Authors: Christopher R Zito; Lucia B Jilaveanu; Valsamo Anagnostou; David Rimm; Gerold Bepler; Sauveur-Michel Maira; Wolfgang Hackl; Robert Camp; Harriet M Kluger; Herta H Chao Journal: PLoS One Date: 2012-02-15 Impact factor: 3.240