[Mechanisms of the antitumor action of gestagens on endometrial cancer].

An attempt was made to elucidate the relationship between the progestational activities and antitumor effects of various steroid hormones in vitro and in vivo. The established cell line (Ishikawa cells) of a human endometrial adenocarcinoma bearing estrogen and progesterone receptors was used in this study. Sixteen kinds of steroid hormones including progesterone, medroxyprogesterone acetate (MPA) and danazol were used in vitro. Each hormone was administered at 20 micrograms/ml continuously from the 4th day of culture and the growth curve was evaluated. The effects of progesterone, MPA and danazol at a dosage of 24 mg/kg/day for 53 days on the tumor induced in athymic nude mice with Ishikawa cells were also evaluated. Three kinds of hormones, progesterone, 16 alpha-methylprogesterone and danazol revealed cytocidal effects on the cells in vitro. There was no relationship between the progestational activity and cytocidal effect of each steroid hormone. On the other hand, no significant tumor regression was observed in vivo, but progesterone and danazol showed a tendency to suppress the growth of the tumor. These results suggest that the cytotoxic properties of progesterone may play a more important role than progestational action the cytocidal effect in vitro. It has been known that MPA had antitumor effects on DMBA-induced mammary cancer in rat and human endometrial cancer. However, MPA did not show a significant antitumor effect either in vitro or against the transplanted tumor in this study. Therefore, it was suggested that the antitumor effect of MPA is not direct action on the tumor cells, but indirect action through the interstitial cells of the target organ.