Author/Authors :
Jebahi، نويسنده , , Abdelghani and Villedieu، نويسنده , , Marie and Pétigny-Lechartier، نويسنده , , Cécile and Brotin، نويسنده , , Emilie and Louis، نويسنده , , Marie-Hélène and Abeilard، نويسنده , , Edwige and Giffard، نويسنده , , Florence and Guercio، نويسنده , , Marika and Briand، نويسنده , , Mélanie and Gauduchon، نويسنده , , Pascal and Lheureux، نويسنده , , Stéphanie and Poulain، نويسنده , , Laurent، نويسنده ,
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.
Keywords :
Ovarian cancer , Mcl-1 , NVP-BEZ235 , BIM , ABT-737 , ERK1/2
