Inhibition of endometrial cancer cell lines by mifepristone (RU 486)

OBJECTIVE: To determine the role of mifepristone (RU 486) ill the growth of endometrial cancer cell lines, and the mechanism associated with this regulation. METHODS: Three endometrial cancer cell lines (Hec-1A, KLE, and RL95-2) were used in this study. Growth inhibition was demonstrated by sulforhodamine B cytotoxicity assay, Mode of inhibition Dy RU 486 teas studied by induction of DNA fragmentation. The effect of RU 486 on steady-state accumulation of the progesterone and glucocorticoid receptors (PRs and GRs, respectively) and apoptosis-associated gene products was studied by Western blotting. RESULTS: We demonstrated a dose-dependent inhibition of growth in all of the three endometrial cancer cell lines. Following treatment with 5.0 mu g/mL of RU 486, there was 39.3%, 66.3%, and 75.5% inhibition of KLE, Hec-1A, nod RL95-2 cells, respectively. Decreased expression of GR in RL95-2 (0.1-10 mu g/mL) and in KLE cells (10 mu g/mL) ions observed. A marked decrease of PR was seen with RL95-2 cells at 10 mu g/mL, there teas no change in the KLE Cells, wand a dose-dependent decrease was seen with Hec-1A cells. Various levels of apoptosis were demonstrated by DNA fragmentation ir till three all lines. Of the genes associated with apoptosis, dose-dependent reduction of bax expression was demonstrated in ECCE cells, while induction of WAF-1 was seen in Hec-1A and RL95-2 cells, nod reduction of bcl-2 was demonstrated ill RL95-2 cells. CONCLUSION: Clinically achievable doses of RU 486 inhibit endometrial cancer cell lines. The mechanism of inhibition involves apoptosis, and regulation of bax, bcl-2, and WAF-1 is demonstrated, Therapeutic application of these findings remains to be determined. Copyright (C) 1998 by the Society for Gynecologic Investigation.