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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 the effect of leptin on the expression of aromatase and estrogen synthesis in situ in endometrial carcinoma (EC) cells and the role of leptin in the pathogenesis of endometrial carcinoma. Methods The co-culture model of EC stromal cells with Ishikawa cells was used in the First Affiliated Hospital of Liaoning Medical University from April 2009 to June 2010. The effects of leptin on the proliferation of EC cells were detected by MTT assay. The expression of leptin was detected by RT-PCR and Western blotting The expression of aromatase mRNA and protein in stromal cells and Ishikawa cells were detected respectively. The effect of leptin on the expression of aromatase in cocultured cells was also observed. The effect of leptin on estradiol production by cocultured cells was detected by radioimmunoassay. Results Leptin significantly promoted the proliferation of mesenchymal endometrial stromal cells and Ishikawa cells co-cultured in a dose-dependent manner in the range of 0-100 μg / L, with the highest proliferation effect at 100 μg / L from (121.14 ± 5.50)% to (274.24 ± 6.03)%. The expression level of aromatase in interstitial cells was higher than that in Ishikawa cells. Leptin increased the expression of aromatase in EC cells and the synthesis of estrogen. When leptin at 100 μg / L, E2 ± 0.17) pmol / L, letrozole inhibited this effect when E2 (0.47 ± 0.18) pmol / L was added with 100 μg / L leptin + 1 μmol / L letrozole. Conclusion Leptin may promote the proliferation of EC cells by increasing the expression of aromatase in EC cells and increasing estrogen synthesis in situ.