Figure 4
From: Resistance to HSP90 inhibition involving loss of MCL1 addiction
MCL1 dependence is lost in cells selected for resistance to ganetespib. (a) Cells selected for resistance (STAR) were tested for cell viability after 72 h treatment with ganetespib compared with parental MSTO-211H. (b) Parental and resistant cells were treated for 48 h with ganetespib 200 nm. On-target activity of ganetespib on Akt and ERK and the effect of HSP90 inhibition on pro- and anti-apoptotic proteins were analysed by western blot. (c) Cytochrome-c release was assessed after 48 h treatment with ganetespib 200 nm in the presence or absence of digitonin. Mitochondrial-free cytosolic fraction has been used for western blot analysis. (d) Resistant cells were transfected with siRNA targeting MCL1 for 48 h. Induction of apoptosis was measured by western blot with PARP antibody.
