雄激素受体对雌激素受体阳性乳腺癌细胞增殖的抑制作用

Androgen receptor inhibits the proliferation of estrogen receptor-positive breast cancer cells

目的雄激素受体(androgen receptor,AR)在乳腺癌中广泛表达,并影响乳腺癌细胞的增殖。文中旨在探讨AR在雌激素受体(estrogen receptor,ER)阳性乳腺癌细胞中的作用。方法选取生长状态良好的MCF-7细胞随机分成3组,分别给予不同的处理,双氢睾酮组:加入双氢睾酮及DMSO溶液;比卡鲁胺组:加入比卡鲁胺及无水乙醇溶液;对照组:无水乙醇及DMSO溶液;保证每组无水乙醇及DMSO溶液浓度相同。用噻唑蓝比色法、细胞计数、流式细胞术观察细胞增殖和凋亡改变,并用免疫印迹检测细胞周期调控相关基因的表达改变。结果免疫印迹结果显示,双氢睾酮组AR相对灰度值(1.055±0.020)较对照组(0.795±0.020)显著升高(P<0.05),而比卡鲁胺组(0.705±0.010)则较对照组明显降低(P<0.05)。流式细胞结果显示:与对照组乳腺癌细胞早期凋亡率[(3.540±0.375)%]相比,双氢睾酮组[(5.120±0.312)%]显著增加(P<0.01),而比卡鲁胺组[(2.410±0.367)%]明显减小(P<0.01)。与对照组比较,双氢睾酮组MCF-7细胞中p53、p73、p21蛋白表达升高,而比卡鲁胺组细胞中p53、p73、p21蛋白表达有所下降,差异有统计学意义(P<0.05)。结论 AR在ER阳性乳腺癌中发挥抑制肿瘤生长的作用,预示AR有可能成为ER阳性乳腺癌治疗的一个潜在靶点。

Objective Androgen receptor（ AR） is extensively expressed in breast cancer and influences the proliferation of the malignant cells. Our study aimed to investigate the effect of AR on estrogen receptor（ ER）-positive breast cancer. Methods ER-positive MCF-7 breast cells were exposed to various concentrations of agonist dihydrotestosterone（ DHT） or antagonist bicalutamide or left untreated. Then the proliferation and apoptosis of the cells were determined by MTT assay,cell counting,and flow cytometry,and the expressions of the proteins related to cell cycle regulation were detected by Western blot. Results The relative gray value of AR was significantly increased in the DHT group（ 1. 055 ± 0. 020） but decreased in the bicalutamide group（ 0. 705 ± 0. 010） as compared with the blank control（ 0. 795 ± 0. 020）（ both P〈 0. 05）. Flow cytometry showed that the early apoptosis rate of the breast cancer cells was markedly higher in the DHT group（ [5. 120 ± 0. 312]%） but lower in the bicalutamide group（ [2. 410 ± 0. 367]%）than in the blank control（ [3. 540 ± 0. 375]%）（ both P 〈0. 01）.In comparison with the control group,the expressions of the p53,p73 and p21 proteins in the MCF-7 cells were remarkably up-regulated in the DHT group but down-regulated in the bicalutamide group（ both P 〈0. 05）. Conclusion AR inhibits the proliferation of ER-positive breast cancer cells,which suggests that it may be a potential therapeutic target for ER-positive breast cancer.