It has been observed that the development of hormone resistance in prostate cancer may be due to the upregulation of antiapoptotic genes, one of which is survivin.
Zhang et al. hypothesize that, if survivin is a significant contributor to the development of hormonal therapy resistance in prostate cancer cells, targeting survivin and blocking it would enhance prostate cancer cell susceptibility to anti-androgen therapy. (Anti-androgen therapy uses drugs to eliminate the presence of androgens in the cell and cellular environment, since such androgens are known to enhance tumour immortality in prostate cancer cells.) Zhang et al. first assessed the level of survivin expression of LNCaP (an androgen-dependent prostate cancer cell line that expresses intact androgen receptors) using quantitative Western analysis and found high expression of survivin in these cells. Cells exposed to dihydrotestosterone (DHT) showed increased levels of survivin expression only and not other IAP family members. This result suggests that androgens may upregulate survivin, which contributes to the resistance to apoptosis observed in the tumour cells. Next, with the addition of flutamide (an antiandrogen) to the cells, survivin levels were observed to significantly decrease. The LNCaP cells were transduced separately with the different constructs of the survivin gene (mutant or wild-type) and subjected to flutamide treatment and assessed for the apoptosis level. Flutamide-treated survivin mutant-transduced cells were shown to significantly increase apoptosis by double that of flutamide treatment alone. On the other end, overexpression of the wild-type survivin was found to significantly reduce the apoptosis levels from flutamide treatment compared to flutamide treatment alone. Therefore, these results support the hypothesis that survivin plays a role in the anti-apoptotic nature of the LNCaP cancer cell line and that inhibiting survivin in prostate cancer cells appears to enhance the therapeutic effect of flutamide.