来曲唑对子宫肌瘤细胞体外增生的作用

目的探讨芳香化酶抑制剂来曲唑对子宫肌瘤细胞芳香化酶P450（P450arom）、雌二醇（E2）表达以及对细胞增生的作用，为子宫肌瘤药物治疗提供实验依据。方法体外培养子宫肌瘤细胞，不同浓度来曲唑干预后，应用四甲基偶氮唑蓝（MTT）法检测细胞增生活性，RT—PCR和免疫细胞化学检测P450arom表达，放射免疫法测定E2含量。结果低浓度（0．06μmol／L）来曲唑对肌瘤细胞P450arom表达和E2分泌无明显影响（P〉0．05），高浓度（0．6～6μmol／L）来曲唑显著降调P450arom表达（P〈0．05），抑制E2生成和肌瘤细胞增生，差异有统计学意义（P〈0．05）。且随着药物浓度递增，抑制作用逐渐增强。结论芳香化酶抑制剂来曲唑以浓度依赖性方式，降调P450arom表达、减少E2生成，抑制肌瘤细胞的体外增生。

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

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.