Multiple Pathways Compensate for Antisense Suppression of Bcl-2 in LNCaP Cells Contributing to Tumor Resistance

Multiple Pathways Compensate for Antisense Suppression of Bcl-2 in LNCaP Cells Contributing to Tumor Resistance

Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth regulatory proteins. While most oligos target growth factors or their receptors, others are directed against apoptosis inhibitors and mediators of androgen action. Those which suppress Bcl-2 activity have even reached clinical trials in prostate cancer patients. We previously evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein Bcl-2. LNCaP cells adapted to this restoration of apoptosis with suppression of caspase-3 (another apoptosis inhibitor). In this continuing study we evaluated additional proteins associated with tumor progression and found the expression of the Androgen Receptor (AR), its p300 and IL-6 co-activators and the v-myc oncogene are enhanced.