Jebahi A.,Normandy University |
Jebahi A.,Biology and Innovative Therapeutics of Locally Aggressive Cancers Unit EA |
Jebahi A.,Francois Baclesse Comprehensive Cancer Center |
Villedieu M.,Normandy University |
And 31 more authors.
Cancer Letters | Year: 2014
We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Here we assessed the anticancer potential of combining ABT-737-induced inhibition of Bcl-xL with Mcl-1 inhibition via PI3K/Akt/mTOR pathway disruption using NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation without inducing apoptosis. It strongly repressed Mcl-1 expression and induced Puma expression in both cell lines tested while differentially modulating Bim between the two. Interestingly, NVP-BEZ235 efficiently sensitized ovarian carcinoma cells to ABT-737, provided that Bim expression was induced. Moreover, inhibiting the ERK1/2 pathway restored Bim expression and sensitized low Bim-expressing cancer cells to the BEZ235/ABT-737 treatment. © 2014 The Authors. Source