Effect of leuprorelin acetate on cell growth and prostate-specific antigengene expression in human prostatic cancer cells

Objectives: We investigated modulation of cell growth and prostate-specific antigen (PSA) gene expression in prostatic cancer cells by the luteinizing hormone-releasing hormone analog (LH-RHa), leuprorelin acetate, alone or c ombined with other agents. Methods: The effect of the analog on proliferati on of both androgen-sensitive and -insensitive prostate cancer cells, maint ained in different culture conditions, was evaluated by cell counts at vari ous intervals of time. Basal expression of PSA gene and its variations were determined by a reverse transcriptase-polymerase chain reaction assay. Res ults: LH-RHa is ineffective in regulating cell growth, when used alone in b oth hormone-sensitive and -insensitive cell lines. Nevertheless, it counter acts the stimulatory action of androgens on proliferation of LNCaP cells, w hich respond to low concentrations of dihydrotestosterone. Moreover, LH-RHa has an inhibitory effect on the mitogenic action of epidermal growth facto r (EGF) in androgen-unresponsive PC-3 cells. The analog reduces PSA gene ex pression in both hormone-sensitive and -insensitive cells. Interestingly, i t counteracts the gene expression induced by androgens in LNCaP cells and b y EGF in PC-3 cells. Conclusions: These data show that LH-RHa may behave li ke a negative growth factor, which directly regulates cell growth and PSA g ene expression. Moreover, our findings support the idea that growth factors may interfere with the androgen signalling pathway.