Effects of castration and androgen replacement on tumour growth of human hepatocellular carcinoma in nude mice.

BACKGROUND/AIMS: Previous clinical investigations suggest that androgen and its receptor (AR) may play an important role in the growth of hepatocellular carcinoma. Few studies are available concerning the effect 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 tumour size and expression of proliferating cell nuclear antigen and Lewis Y antigen were examined in intact males, castrated males, intact females, and castrated males with androgen replacement. AR of the tumour was measured with binding assay, ultracentrifugation, and Western blotting.

RESULTS

The growth of SM10 was significantly better in intact males and castrated males with 5a-dihydrotestosterone injection than in intact females and castrated males. Castration did not suppress the growth of SM2. The tumour AR level was reduced by castration but maintained by the hormone substitution. Although proliferating cell nuclear antigen expression was closely associated with tumour growth, Lewis Y antigen expression did not differ among the groups.

CONCLUSIONS

These data may indicate that this hepatocellular carcinoma subline (SM10) is androgen-responsive and that androgen ablation can cause the inhibition of the tumour growth, which might be due to decreased proliferative and not increased apoptotic activities. In addition, such androgen-stimulated tumour growth seems to be mediated through AR.