BCL2 antisense reduces prostate cancer cell survival following irradiation

Irradiation of the prostate, delivered as external beam radiation therapy (EBRT), is currently one of the few treatment options for localized prostate cancer. While it is relatively effective, the failure rate still remains unacceptably high with a 5-year biochemical failure rate of 10-40%. Utilizing genetically engineered LNCaP prostate cancer sublines that either overexpress Bcl2 (LNCaP/S22-d) or have down-regulated Bcl2 (LNCaP/AS17-f) we investigated the influence of this antiapoptotic protein on clonogenic survival following radiation. The radiation dose response curves (2-8 Gy)for the sublines differed significantly from the parental LNCaP (LNCaP/S22d: p < 0.001 and LNCaP/AS17-f: p = 0.008). The relative survival of the sublines revealed increased survival in the Bcl2 overexpressing cells, and decreased survival in the Bcl2 down-regulated cells. These data suggest a potentially important therapeutic approach for enhancing radiosensitivity in prostate tumors via antisense oligonucleotide or other drug therapies that down-regulate Bcl2. Strategies such as these likely hold the promise of enhancing the efficacy of EBRT by decreasing tumor cell survival, reducing the incidence of tumor recurrence and improving patient outcome.