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.