Yu L, Nagasue N, Makino Y, Nakamura T
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
J Hepatol. 1995 Mar;22(3):295-302. doi: 10.1016/0168-8278(95)80282-7.
BACKGROUND/AIMS: Little is known about genuine roles of androgens and their receptor in hepatocellular carcinoma.
In the present study, two sublines derived from a human hepatocellular carcinoma cell line KYN-1 were used: KYN-1/SM10 with androgen receptor and KYN-1/SM2 without androgen receptor.
The binding assay with 3H-R1881 identified the presence of both cytosolic and nucleosolic androgen receptors in KYN-1/SM10 but not in KYN-1/SM2. In serum-free medium, dihydrotestosterone was able to enhance the cell proliferation and 3H-thymidine incorporation in androgen receptor positive KYN-1/SM10 cells. Such effects of dihydrotestosterone were partially inhibited by an antiandrogen cyproterone acetate in a concentration-dependent manner. On the other hand, the growth of androgen receptor negative KYN-1/SM2 cells was not influenced by dihydrotestosterone and cyproterone acetate at all. When dihydrotestosterone was removed from the medium of KYN-1/SM10 cultures, the nucleosolic androgen receptor decreased to undetectable levels within 8 h and the cytosolic androgen receptor within 48 h. Addition of dihydrotestosterone (10 nM) to the cells that had been deprived of dihydrotestosterone for 24 h partially restored both cytosolic and nucleosolic androgen receptor within 12 h.
The current results seem to indicate that the growth of androgen receptor positive human hepatocellular carcinoma may be enhanced with androgen through androgen receptors and that antiandrogen therapy with cyproterone acetate may be effective in the treatment of androgen receptor-positive hepatocellular carcinoma.
背景/目的：关于雄激素及其受体在肝细胞癌中的真正作用，人们了解甚少。
在本研究中，使用了源自人肝癌细胞系KYN-1的两个亚系：具有雄激素受体的KYN-1/SM10和没有雄激素受体的KYN-1/SM2。
用³H-R1881进行的结合试验表明，KYN-1/SM10中存在胞质和核雄激素受体，而KYN-1/SM2中不存在。在无血清培养基中，双氢睾酮能够增强雄激素受体阳性的KYN-1/SM10细胞的增殖和³H-胸腺嘧啶核苷掺入。双氢睾酮的这种作用被抗雄激素醋酸环丙孕酮以浓度依赖的方式部分抑制。另一方面，雄激素受体阴性的KYN-1/SM2细胞的生长完全不受双氢睾酮和醋酸环丙孕酮的影响。当从KYN-1/SM10培养物的培养基中去除双氢睾酮时，核雄激素受体在8小时内降至无法检测的水平，胞质雄激素受体在48小时内降至无法检测的水平。向已剥夺双氢睾酮24小时的细胞中添加双氢睾酮（10 nM）可在12小时内部分恢复胞质和核雄激素受体。
目前的结果似乎表明，雄激素受体阳性的人肝癌的生长可能通过雄激素受体被雄激素增强，并且用醋酸环丙孕酮进行抗雄激素治疗可能对雄激素受体阳性的肝细胞癌治疗有效。
