Inhibitory effects of danazol and medroxyprogesterone acetate on [3H]thymidine incorporation in human endometrial cancer cells.
Effects of medroxyprogesterone acetate (MPA) and danazol (1 nM-10 microM) on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were simultaneously investigated. Of twenty-four endometrial adenocarcinomas examined, five tumors were successfully maintained in primary cell culture. The addition of MPA as well as danazol in culture of cells from the five tumors resulted in a significant inhibition of [3H]thymidine incorporation in cancer cells from three tumors having progesterone receptors (PR). The minimum effective concentrations of MPA and danazol for the inhibition of [3H]thymidine incorporation were found to be 10 and 100 nM, respectively. The difference in effective concentration could be explained by a higher affinity of MPA to PR than that of danazol in cancer cells. On the other hand, neither danazol nor MPA affected [3H]thymidine incorporation in cultured cells from the remaining two tumors, in which PR was absent in one but present in the other. These findings, together with our previous findings that danazol inhibited the growth of a human endometrial cancer cell line with PR, suggest that a growth-inhibitory effect of danazol on human endometrial cancer cells is mediated through PR in the cells.
Terakawa
N
N
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Ikegami
H
H
Shimizu
I
I
Inoue
M
M
Tanizawa
O
O
Matsumoto
K
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D003613:Danazol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D011245:Pregnadienes / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D011245:Pregnadienes; D011980:Receptors, Progesterone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D003613:Danazol; D013936:Thymidine