目的 分析BMI-1抑制剂PTC-596对人乳腺癌MCF-7细胞增殖、周期和凋亡的影响。 方法 以人乳腺癌MCF-7细胞为肿瘤细胞模型，正常培养为阴性对照组，25、50 nmol/L PTC-596处理SGC-7901细胞48 h为低、高药物浓度实验组。利用CCK8法分析细胞增殖能力；流式细胞术分别结合PI单染、DCFH-DA探针、JC-1探针以及PI/FITC-Annexin V双染分析细胞周期、活性氧（reactive oxygen species， ROS）累积、线粒体膜电位和凋亡细胞比例；Western blot法检测细胞BIM-1蛋白和周期相关蛋白CyclinD1、CyclinB1、P21以及凋亡相关蛋白Bax、Bcl-2、c-PARP蛋白相对表达水平。 结果 与对照组相比，PTC-596高效抑制人乳腺癌MCF-7细胞的增殖，处理48 h后IC₅₀ 为（49.33 ± 7.02）nmol/L。低、高药物浓度实验组细胞中BMI-1表达显著减少（P < 0.01）。实验组细胞中CyclinB1和P21相对表达增加，CyclinD1表达减少，细胞有丝分裂被抑制，出现G₂/M期周期阻滞；同时活性氧累积增多，线粒体膜电位下降，Bax表达上调，Bcl-2表达下调，c-PARP增加，凋亡细胞比例从2.04%显著上升为10.56%、26.74%。与对照组相比较，以上结果差异均有统计学意义（P < 0.05）。 结论 PTC-596高效杀伤人乳腺癌MCF-7细胞，其机制可能与抑制BMI-1、诱导细胞周期阻滞和内源性线粒体途径细胞凋亡密切相关。

Objective To investigate the effect of a novel BMI-1 inhibitor PTC-596 on the proliferation， cell cycle， and apoptosis of human breast cancer MCF-7 cells. Methods MCF-7 cells treated with 0 nmol/L PTC-596 were used as control group； MCF-7 cells treated with 25， and 50 nmol/L PTC-596 as experimental group. The CCK8 assay was used to evaluate the celular proliferation ability； DCFH-DA probe/flow cytometry （FCM） was performed to detect the change of cellular reactive oxygen species （ROS）. PI single-staining/FCM was used to analyze cell cycle； PI/FITC -Annexin V/FCM to analyze the proportion of apoptotic cells. JC-1/FCM was performed to detect the change of mitochondrial membrane potential（MMP）； western blot to analyze the expression of BMI-1， cell cycle related proteion（CyclinD1， CyclinB1， and P21） and apoptosis related proteion （Bax， Bcl-2， and c-PARP）. Results PTC-596 could significantly inhibit MCF-7 cell proliferation， with the IC₅₀ value of 49.33 ± 7.02 nmol/L（24 h）. BMI-1 expression was significantly decreased in the low- and high- drug concentration experimental group （P < 0.01）. The relative expression of CyclinB1 and P21 in the experimental groups were increased （P < 0.01）， while the expression of CyclinD1 was decreased （P < 0.01）， and cell mitosis was inhibited （P < 0.01）， resulting in G₂/M cycle arrest （P < 0.01）. At the same time， the accumulation of reactive oxygen species was increased （P < 0.01）； mitochondrial membrane potential was decreased （P < 0.01）. Bax expression was up-regulated （P < 0.01）， while Bcl-2 expression was down-regulated （P < 0.01）； c-PARP was increased （P < 0.01）， and the proportion of apoptotic cells was significantly increased from 2.04% to 10.56% and 26.74% （P < 0.01）. Conclusion PTC-596 can effectively inhibit the proliferation of human breast cancer MCF-7cells， and its mechanism may be closely related to the inhibition of BMI-1， the induction of cell cycle arrest， and the endogenous mitochondrial apoptosis.