目的：探讨中药地黄提取物梓醇（Cat）对乳腺癌MCF-7细胞增殖与凋亡，以及裸鼠移植瘤生长的影响及其机制。方法：以不同质量浓度（0、5、25、50、100、200 μg/mL）Cat 处理人乳腺癌MCF-7细胞，用MTT法筛选Cat 给药浓度。将MCF-7细胞分为空白对照组、Cat 低剂量组、Cat 中剂量组、Cat 高剂量组、Cat+sh-NC 组和Cat+sh-FOXO3组，采用Edu 细胞增殖实验、平板克隆实验、流式细胞术分别检测各组细胞的增殖与克隆形成能力、凋亡率和细胞周期，WB法检测各组细胞中FOXO3、FOXM1、caspase-3和caspase-8 蛋白表达。构建乳腺癌MCF-7 细胞裸鼠移植瘤模型，观察Cat 对移植瘤生长的影响，WB 法检测移植瘤组织中FOXO3和FOXM1蛋白表达。结果：Cat 低（50 μg/mL）、中（100 μg/mL）、高（200 μg/mL）剂量处理的MCF-7细胞的增殖能力均显著下降（均P<0.05）。与空白对照组比较，Cat 低、中、高剂量组Edu阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著降低（均P<0.05），细胞凋亡率、G0/G1 期细胞比例及FOXM1、caspase-3 、caspase-8 蛋白表达均显著升高（均P<0.05）；与Cat+sh-NC 组比较，Cat+sh-FOXO3组Edu 阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著升高（均P<0.05），细胞凋亡率、G0/G1 期细胞比例及FOXM1、caspase-3 和caspase-8 蛋白表达均显著下降（均P<0.05）。Cat 组MCF-7细胞裸鼠移植瘤体积、质量和FOXO3蛋白表达均显著降低（均P<0.05），FOXM1的蛋白表达显著升高（P<0.05）。结论：Cat 抑制乳腺癌MCF-7 细胞增殖并促进凋亡，在体内抑制裸鼠移植瘤的生长，其机制可能与上调FOXO3、下调FOXM1 的表达有关。

Objective: To investigate the effects and the mechanisms of catalpol (Cat) , a herbal extract from rehmannia glutinosa, on the proliferation and apoptosis of MCF-7 cells and the growth of transplanted tumors in nude mice. Methods: Human breast cancer MCF-7 cells were treated in vitro with Cat of different mass concentrations (0, 5, 25, 50, 100, 200 μg/mL), and the concentration of Cat was screened by MTT method. MCF-7 cells were divided into blank control group, Cat low-dose group, Cat medium-dose group, Cat high-dose group, Cat+sh-NC group and Cat+sh-FOXO3 group. Edu cell proliferation assay, plate cloning assay and flow cytometry were used to detect cell proliferation and clonogenetic abilities, the apoptosis rate and the cell cycle in each group, respectively. The protein expressions of FOXO3, FOXM1, caspase-3 and caspase-8 in cells of each group were detected by WB. A nude mouse transplant model of breast cancer MCF-7 cells was constructed to observe the effects of Cat on the growth of transplanted tumors. The protein expressions of FOXO3 and FOXM1 in transplanted tumor tissues were detected by WB. Results: The proliferation ablities of MCF-7 cells treated with low (50 μg/mL), medium (100 μg/mL) and high (200 μg/mL) Cat doses decreased significantly (all P<0.05). Compared with blank control group, the Edu positive cell rate, the number of clones formed, S phase and G2/M phase cell ratio and FOXO3 protein expression in Cat low, medium and high dose groups decreased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 increased significantly (all P<0.05). Compared with those of Cat+sh-NC group, the Edu positive cell rate, the colony formation number, S phase to G2/M phase cell ratio and FOXO3 protein expression of Cat+sh-FOXO3 group increased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 decreased significantly (all P<0.05). In Cat group, the volume and weight of nude mouse transplant MCF-7 cell tumors and the protein expression of FOXO3 decreased significantly (all P<0.05), while the protein expression of FOXM1 increased significantly (P<0.05). Conclusion: Cat inhibits the proliferation and promotes the apoptosis of breast cancer MCF-7 cells and inhibits the growth of transplanted tumors in nude mice. The mechanisms may be related to the upregulation of FOXO3 expression and the downregulation of FOXM1 expression.

山东省医药卫生科技发展计划（No. 2016WS0627）