[Progestogen therapy in the treatment of endometrial cancer--clinical results and mechanism of steroid action].
The use of medroxyprogesterone acetate (MPA) in therapy of patients with endometrial cancer has been recently examined by the Japan Gynecological Cancer Treatment Group. The response rate of oral MPA was 23.6% (13/55 evaluables) and the average period up to the onset of response was 15.2 weeks (4-28 wks). The response rate was higher in well-differentiated tumors than in poorly differentiated ones. Although it is well known that steroid hormone action is mediated by steroid hormone receptor, the presence of progesterone receptor in cancer tissue seems to be not absolutely necessary for the responsibility to MPA, a potent progestational compound. The reason was studied, in vitro, in our laboratory by using the technique of human tumor clonogenic assay. In this system, MPA showed a marked suppressive effect on the colony formation of endometrial cancer cells. Similar effects were also observed with progesterone, 17 alpha-hydroxyprogesterone caproate and megestrol acetate. Norethindrone and norgestrel, which are both potent progestational compounds, showed almost no anticancer activity on Ishikawa cell in this in vitro system. It became clear that progestational activity was not always associated with anticancer activity, and norethindrone had no influence on the inhibitory effect of MPA, although norethindrone has a strong affinity for progesterone receptor. Similarly, RU 486, which is known as a potent antiprogestogen agent and has a high affinity to progesterone receptor, did not influence the effect of MPA. These results clearly indicated that the anticancer activity of MPA was not mediated by high affinity low capacity progesterone receptor, and a pharmacological effect must be considered for understanding the effect of MPA on endometrial cancer.
Okada
H
H
Dept. of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine.
D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D015735:Mifepristone; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009640:Norethindrone / Q000494:pharmacology; D009644:Norgestrel / Q000494:pharmacology; D045167:Progesterone Congeners / Q000627:therapeutic use*; D011980:Receptors, Progesterone / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D014594:Uterine Neoplasms / Q000188:drug therapy*
D004963:Estrenes; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D015735:Mifepristone; D009644:Norgestrel; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D009640:Norethindrone