Effect of antiandrogen treatment on chemical hepatocarcinogenesis in rats.
We studied the effect of antiandrogen treatment on the Solt-Farber model of hepatocarcinogenesis in male Sprague-Dawley rats. The size and number of the liver tumors were reduced by various antiandrogen treatments (orchiectomy, an LH-RH analog, and chlormadinone acetate). In addition, the proportion of poorly differentiated carcinomas was decreased by the antiandrogen treatment, while that of well-differentiated trabecular or glandular carcinomas was increased. The bromodeoxyuridine labeling index of the tumor cells was significantly decreased after the antiandrogen treatment. The expression of rat androgen receptor mRNA in carcinoma tissue was increased when compared to control liver tissue, and was decreased after the antiandrogen treatment. Orchiectomy had the greatest inhibitory effect on carcinoma, although the effect of chemical orchiectomy using an LH-RH analog was almost similar to that of orchiectomy. These results suggest that the clinical application of antiandrogen therapy for human hepatocellular carcinoma might be possible in the future.
Matsuura
B
B
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Taniguchi
Y
Y
Ohta
Y
Y
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D002715:Chlormadinone Acetate / Q000494:pharmacology*; D004195:Disease Models, Animal; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D009919:Orchiectomy; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics
D000726:Androgen Antagonists; D012333:RNA, Messenger; D011944:Receptors, Androgen; D002715:Chlormadinone Acetate; D007987:Gonadotropin-Releasing Hormone