瘦素对人子宫内膜癌细胞雌激素原位合成的影响

Effect of leptin on the local estrogen synthesis in human endometrial carcinoma cells

目的探讨瘦素对子宫内膜癌(EC)细胞中芳香化酶表达和原位雌激素合成的影响,以及瘦素在子宫内膜癌发病机制中的作用。方法 2009年4月至2010年6月在辽宁医学院附属第一医院采用EC间质细胞与Ishikawa细胞共培养模式;MTT法检测瘦素对EC细胞增殖的影响;RT-PCR法及免疫印迹法分别检测间质细胞和Ishikawa细胞中芳香化酶mRNA及蛋白的表达,并观察瘦素对共培养细胞中芳香化酶表达的影响;放免法检测瘦素对共培养细胞生成雌二醇的影响。结果瘦素明显促进共培养的子宫内膜癌间质细胞和Ishikawa细胞的增殖,在0～100μg/L范围内呈剂量依赖性,100μg/L时增殖效应最大,自(121.14±5.50)%至(274.24±6.03)%;芳香化酶在间质细胞中的表达水平高于Ishikawa细胞,瘦素增加EC细胞芳香化酶的表达及雌激素的合成,当100μg/L瘦素时,E2(1.35±0.17)pmol/L,当加入100μg/L瘦素+1μmol/L来曲唑时E2(0.47±0.18)pmol/L,来曲唑可抑制此作用。结论瘦素可能通过促进EC细胞芳香化酶的表达,增加原位雌激素合成进而刺激EC细胞增殖。

Objective To investigate whether leptin was able to stimulate aromatase expression in endometrial carcinoma cells, addressing its potential role in enhancing local estrogen production. Methods Between Apr 2009 and Jun 2010, we employed cocuhure system using Ishikawa and stromal cells isolated from endometrial carcinomas in the First Affiliated Hospital of Liaoning Medical College. The effect of leptin on cell proliferation was assayed by MTT method. Aromatase mRNA and proteins content were analyzed by the reverse transcription-PCR method and western blot analysis respectively,Aromatase production assays were done on cells treated or non-treated with leptin. Concentration of estradiol （ E2 ） was measured by Radioimmunoassy. Results The endonletrial cancer cells showed a dramatic increase in growth after treatment with leptin. Aromatase was not only highly expressed in the stromal cells but also in Ishikawa cells. Leptin enhanced P450arom mRNA and protein expression as well as estrogen production in endometrial carcinoma cells. It is noteworthy that this phenomenon was completely reversed by the aromatase inhibitor letrozole. Conclusion Leptin can stimulate aromatase expression in endometrial carcinoma cells, addressing its potential role in enhancing local estrogen production and thereby inducing tumor cell growth stimulation.