Docetaxel and a novel bcl-2 antisense oligonucleotide for enhanced apoptosis in prostate cancer cells: A potential therapeutic strategy

Background: Prostate cancer is a leading cause of morbidity and mortality among men. Overexpression of Bcl-2 proteins is linked to prostate cancer progression, suggesting that targeting Bcl-2 could enhance therapeutic efficacy. Therefore, Bcl-2 inhibition may potentiate anti-tumor activity in prostate cancer. Methods: We designed a novel antisense oligonucleotide (ASO) derived from G3139 and evaluated its anti-proliferative effects in LNCaP and PC3 prostate cancer cell lines. The apoptotic effects of docetaxel (DTX) and the ASO, administered alone or in combination, were assessed by real-time PCR and Annexin V-FITC/PI flow cytometry. We hypothesized that the combination therapy would be more effective than either agent alone. Results: The ASO significantly down-regulated Bcl-2 mRNA and inhibited proliferation in both cell lines, as shown by real-time PCR. Flow cytometry revealed an increase in early apoptotic cells in all treated groups. Co-treatment with the ASO and DTX produced the highest apoptotic rates (75–85 %). Conclusions: The novel ASO effectively reduces Bcl-2 expression and sensitizes prostate cancer cells to docetaxel, permitting lower DTX doses. The combination therapy induced 75–85 % apoptosis in LNCaP and PC3 cells, suggesting an improved strategy that may limit high-dose DTX–associated resistance and toxicity.