No compensation in CD44 stem cell marker following BCL-2 suppression by antisense oligonucleotides

Antisense oligonucleotides have previously been used to target regulatory proteins in prostate cancer models. We evaluated mono- and bispecific oligonucleotides which comparably suppressed expression of B-cell lymphoma-2 (BCL-2) in LNCaP cells. Cells compensated by suppressing caspase-3 (an apoptosis promoter), and enhancing the expression of androgen receptor and co-activating p300 and interleukin-6 (IL-6) proteins. This suggests that increased androgen sensitivity accompanies BCL-2 suppression with a pattern associated with more advanced tumors. To further evaluate tumor resistance and compensatory mechanisms we evaluated the stem cell-associated CD44 expression and found it to be unaffected by treatment, suggesting that this tumor population is not activated or expanded by suppressive BCL-2 therapy.