GSK-3β activity and p53 levels (HDM2 blockade) determine whether sorafenib exposure downmodulates Bcl-2 and Bcl-x
in melanoma cells. (Left Panel). A375 cells stably transfected with a tetracycline-inducible GSK-3β shRNA were first treated with doxycycline (or not) and then exposed to sorafenib and/or MI-319. Cell lysates were then probed for Bcl-2 and Bcl-xL. (Right Panel). SKMEL5 and SKMEL5-GSK-3βS9A cells were treated with sorafenib and MI-319 and the cell lysates then probed for Bcl-2 and Bcl-xL.