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

摘要

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 com-pared 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 ([51.20 ±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-posi-tive breast cancer cells , which suggests that it may be a potential ther-apeutic target for ER-positive breast cancer .%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。