Mechanism of antitumoral activity of medroxyprogesterone acetate for endometrial cancer.
The colony-formation of Ishikawa cells, which originate from well differentiated endometrial cancer, and produce progestogen receptors (PR), was inhibited by high concentrations of medroxyprogesterone acetate (MPA). However, the colony-formation was not inhibited by norethindrone (ENT), as a luteohormone or 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl-1)-17 alpha(prop-1-ynyl)-estra-4, 9-dien-3-one (RU-486), as an antiprogestogen. Colony-formation in cells treated with MPA alone was not significantly different from that in those treated with MPA combined with either ENT or RU-486. ENT and RU-486 have high affinity with PR as does MPA. If the suppressive effect by MPA on colony-formation is mediated via PR, then this suppression should be competitively inhibited by ENT or RU-486. Our findings indicate that the effect of MPA is not mediated via PR.
Fujimoto
J
J
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine.
Fujita
H
H
Hosoda
S
S
Okada
H
H
D000970:Antineoplastic Agents; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D015735:Mifepristone / Q000494:pharmacology; D009640:Norethindrone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D011980:Receptors, Progesterone; D015735:Mifepristone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D009640:Norethindrone