We describe an in vitro model for prostate cancer treatment that sugge
sts a potential benefit for combined androgen ablation and cytotoxic c
hemotherapy. Androgen treatment of the LNCaP hormone-dependent human p
rostate cancer cell line induces increased expression of the BCL-2 pro
tein. Increased levels of this protein are known to mediate inhibition
of apoptosis. LNCaP cells, however, did not undergo apoptosis in resp
onse to androgen withdrawal. Etoposide exerts its cytotoxicity on LNCa
P and other cells by inducing apoptosis. In vitro etoposide cytotoxici
ty was diminished 83% in the presence of either 10(-8) M dihydrotestos
terone or 10(-9) M R1881 in LNCaP cells. The interaction between andro
gen and etoposide was mediated through the BCL-2 protein, since bcl-2
antlsense oligonucleotides blocked the protective effect of androgens
on etoposide cytotoxicity.