目的：探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法：利用不同浓度的贝母素乙处理人结肠癌细胞HCT116 和正常结肠上皮细胞CCD841 CON，通过CCK-8 法和结晶紫染色法检测贝母素乙对HCT116 和CCD841 CON细胞增殖活力的影响，流式细胞术和WB法检测贝母素乙对HCT116 细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型，观察贝母素乙对小鼠模型肿瘤生长和OS的影响，免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果：贝母素乙可显著抑制结肠癌HCT116 细胞的增殖能力（P<0.01），诱导HCT116 细胞周期G0/G1 期阻滞（P<0.01），降低CDK4、CDK6和cyclin D1的蛋白表达水平（均P<0.01）。荷瘤小鼠实验结果显示，贝母素乙（0.75 mg/kg）显著抑制HCT116 细胞移植瘤的生长并延长荷瘤裸鼠的OS（P<0.05 或P<0.01），降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积，下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达（P<0.01或P<0.05）。结论：贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平，引起细胞周期G0/G1期阻滞，从而抑制结肠癌HCT116细胞的增殖。

Objective: To explore the inhibitory effects and molecular mechanism of peiminine on colon cancer HCT116 cells.Methods: Human colon cancer HCT116 cells and normal colon epithelial CCD841 CON cells were treated with various concentrations of peiminine. The effects of peiminine on the proliferative vitality of HCT116 and CCD841 CON cells were detected by CCK-8 method and crystal violet staining. The effects of peiminine on the cell cycle and the expression of cycle related proteins in HCT116 cells were detected by flow cytometry and Western blot. HCT116 nude mouse transplantation tumor model and the AOM/DSS-induced colon cancer mouse model were constructed to observe the effects of peiminine on tumor growth and overall survival in the mouse model. The effects of peiminine on the expressions of cell cycle related proteins CDK4, CDK6 and cyclin D1 in transplanted tumors or tumor tissues were detected by immunohistochemistry and Western blot. Results: Peiminine significantly inhibited the proliferation ability (P<0.01), induced the G0/G1 phase arrest (P<0.01), and reduced the expression levels of CDK4, CDK6, and cyclin D1 proteins HCT116 cells (all P<0.01). The results of tumor bearing nude mice showed that peiminine (0.75 mg/kg) significantly inhibited the growth of HCT116 cell transplanted tumors, increased the overall survival rate (P<0.05 or P<0.01）. Peiminine also reduced the weight and prolonged the overall survival of AOM/DSS model mice, reduced the number and volume of tumors in cancerous colon tissues, and down-regulated the expressions of CDK4, CDK6 and cyclin D1 proteins in tumor tissues（P<0.05 or P<0.01）. Conclusion: Peiminine can cause cell cycle G0/G1 phase arrest, and thus suppress the proliferation of colon cancer HCT116 cells through downregulating the expression levels of CDK4, CDK6, and cyclin D1.

吉林省科技发展计划（No. 20220508075RC）；长春市科技发展计划项目创新平台与人才计划青年科技人才创新创业专项（No. 21QC01）；吉林省中医药科技项目（No. 2024255）