Down-regulation of PKCη or Bcl-xL, but not Bcl-2, potentiates the cytotoxic effects of TRAIL in prostate cancer cells

TRAIL is a promising candidate for the treatment of cancer. However, some tumours display resistance to TRAIL, prompting us to explore whether the apoptotic responsiveness of cancer cells to TRAIL could be enhanced by targeting the novel PKC isoform η, Bcl-2 and Bcl-xL. Transfection of PC-3 cells with second-generation antisense oligonucleotides caused a significant knockdown of the corresponding mRNAs and proteins as revealed by real-time RT-PCR and Western blot analyses. Knockdown of either PKCη or Bcl-xL, but not Bcl-2, and administration of TRAIL significantly synergised in inducing apoptosis (as evidenced b…