Citation
- Authors: Jebahi, A., Villedieu, M., Petigny-Lechartier, C., Brotin, E., Louis, M. H., Abeilard, E., Giffard, F., Guercio, M., Briand, M., Gauduchon, P., Lheureux, S., Poulain, L.
- Year: 2014
- Journal: Cancer Lett 348 38-49
- Applications: in vitro / siRNA / INTERFERin
- Cell types:
- Name: IGROV1-R10
- Name: SK-OV-3
Description: Human ovary carcinoma cells
Known as: SKOV3, SKOV-3
Method
20 nM
Abstract
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.