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目的:探讨他莫昔芬、来曲唑、甲地孕酮抑制子宫内膜癌RL95-2细胞生长的机制。方法:体外培养人子宫内膜癌RL95-2细胞(购于中国科学院细胞库)，用不同浓度的他莫昔芬、来曲唑、甲地孕酮处理细胞，并分别设置空白对照组，采用细胞计数试剂盒-8(CCK-8)检测细胞的增殖活性，采用细胞周期及凋亡试剂盒流式细胞术检测细胞周期分布及细胞凋亡情况，蛋白质印迹法检测药物对细胞内磷酸化AKT(p-AKT)蛋白表达的影响。对比各组细胞的增殖活性、周期分布、细胞凋亡及p-AKT蛋白表达情况。结果:CCK-8法检测结果显示，经不同浓度他莫昔芬、来曲唑、甲地孕酮作用后，各药物组的细胞增殖情况与阴性对照组比较均受到明显抑制，且随着药物浓度的增高，抑制作用逐渐增强(n P<0.05)。流式细胞周期分析显示，与空白对照组比较，他莫昔芬组G0/G1期细胞比例下降，S期细胞比例升高(n P<0.05)；甲地孕酮组G0/G1期细胞比例下降，S期细胞及G2/M期比例升高(n P0.05)。凋亡实验结果显示，甲地孕酮组、来曲唑组及他莫昔芬组细胞凋亡率高于空白对照组(n P<0.05)，且甲地孕酮组凋亡率高于来曲唑组、他莫昔芬组(n P<0.05)。以AKT的磷酸化程度作为衡量PI3K/AKT信号通路的活性指标，结果显示，他莫昔芬组、来曲唑组、甲地孕酮组的细胞内p-AKT蛋白表达水平均达到有效抑制，与空白对照组比较，差异有统计学意义(n P<0.05)。n 结论:适宜浓度的他莫昔芬、来曲唑及甲地孕酮均可抑制人子宫内膜癌RL95-2细胞增殖，促进细胞凋亡，他莫昔芬及甲地孕酮能够改变细胞周期分布，且3种药物发挥上述作用可能是通过抑制PI3K/AKT信号通路活化而实现。“,”Objective:To investigate the inhibitory effects of tamoxifen, letrozole and megestrol on the growth of endometrial cancer cell line RL95-2.Methods:Human endometrial carcinoma RL95-2 cells were cultured in vitro and treated with different concentrations of tamoxifen, letrozole, and megestrol. And the blank control group was set up. Cell counting kit-8 (CCK-8) was used to detect the cell proliferation activity. Cell cycle and apoptosis kit flow cytometry was used to detect cell cycle distribution and apoptosis. Western blotting was used to detect the effect of drugs on the expression of intracellular phosphorylated AKT (p-AKT) protein. The proliferation activity, cell cycle distribution, apoptosis, and p-AKT protein expression of each group were compared.Results:The results of CCK-8 assay showed that the cell proliferation of every group was significantly inhibited, compared with the control group after different concentrations of tamoxifen, letrozole, and megestrol; and the inhibitory effect gradually increased, with the increase of drug concentration (n P<0.05). Flow cytometry analysis showed that, compared with the control group, the proportion of G0/G1 phase cells in tamoxifen group decreased (n P<0.05), and the proportion of S phase cells and G2/M phase cells in megestrol group decreased (n P0.05). The results of apoptosis experiment showed that apoptosis rates of megestrol group, letrozole group, and tamoxifen group were higher than that of blank control group (n P<0.05); and the apoptosis rate of megestrol group was higher than that of letrozole group and tamoxifen group (n P<0.05). The phosphorylation of AKT was used as an indicator to measure the activity of PI3K/AKT signaling pathway. The results showed that the expression of p-AKT protein in tamoxifen group, letrozole group, and megestrol group was effectively inhibited, and the difference was statistically significant, compared with the control group (n P<0.05).n Conclusions:Appropriate concentrations of tamoxifen, letrozole, and megestrol can inhibit the proliferation of human endometrial cancer RL95-2 cells, and promote apoptosis. Tamoxifen and megestrol both can change the cell cycle distribution. And the three drugs may take effects by inhibiting the activation of PI3K/AKT signaling pathway.