EFFECTS OF CASTRATION AND ANDROGEN REPLACEMENT ON TUMOR-GROWTH OF HUMAN HEPATOCELLULAR-CARCINOMA IN NUDE-MICE

Background/Aims: Previous clinical investigations suggest that androge n and its receptor (AR) may play an important role in the growth of he patocellular carcinoma, Few studies are available concerning the effec t of androgen manipulation on the growth of AR-positive hepatocellular carcinoma in vivo. Methods: AR-positive (SM10) and AR-negative (SM2) sublines derived from a human hepatocellular carcinoma line KYN-1 were implanted subcutaneously in the lower abdomen of nude mice, The tumou r size and expression of proliferating cell nuclear antigen and Lewis Y antigen were examined in intact males, castrated males, intact femal es, and castrated males with androgen replacement, AR of the tumour wa s measured with binding assay, ultracentrifugation, and Western blotti ng, Results: The growth of SM10 was significantly better in intact mal es and castrated males with Sa-dihydrotestosterone injection than in i ntact females and castrated males. Castration did not suppress the gro wth of SM2, The tumour AR level was reduced by castration but maintain ed by the hormone substitution, Although proliferating cell nuclear an tigen expression was closely associated with tumour growth, Lewis Y an tigen expression did not differ among the groups, Conclusions: These d ata may indicate that this hepatocellular carcinoma subline (SM10) is androgen-responsive and that androgen ablation can cause the inhibitio n of the tumour growth, which might be due to decreased proliferative and not increased apoptotic activities. In addition, such androgen-sti mulated tumour growth seems to be mediated through AR.