Effect of letrozole on the proliferation of uterine leiomyoma cells in vitro.

Abstract

Objective To investigate the expression of aromatase cytochrome P450 (P450arom), the secretion of estradiol and the suppressive effect of aromatase inhibitor letrozole on the proliferation of uterine leiomyoma cells in vitro. Methods Uterine leiomyoma cells were cultured in vitro, after the action of letrozole with different concentration, MTT was used to examine the proliferative activity of uterine leiomyoma cells, RT-PCR and immunocytochemistry was used to determine the expression of the P450arom protein and mRNA, and the concentration of estradiol in media supernatant was measured by radioimmunity. Results Low dosage (0.06 μmol/L) of letrozole had no effect on the expression of P450arom protein and mRNA, and estradiol synthesis in uterine leiomyoma cell (P>0.05). However, high dosage(0,6-6 μmol/L) of letrozole could down-regulate the expression of P450arom, and to inhibit estradiol synthesis and the proliferation activity of uterine leiomyoma cells(P<0.05). Furthermore, the inhibition were shown to decline gradually along with the increase in the concentrations of letrozole. Conclusion The aromatase inhibitor letrozole could suppress the proliferation of uterine leiomyoma cells in the dosage-dependent manner by down-regulating the expression of the P450arom and decreasing the estradiol synthesis, suggesting that the drug may possibly be effective in the clinical treatment of uterine leiomyoma. Key words: Uterine neoplasms; Letrozole; Aromatase; Estradiol