贝母素乙通过诱导G0/G1期阻滞抑制结肠癌细胞的增殖OA北大核心CSTPCD

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 in 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.