仙鹤草内酯通过Wnt/β-catenin信号通路抑制前列腺癌细胞的增殖和侵袭  

Inhibition of prostate cancer cell proliferation and invasion by agrimonolide via the Wnt/β-catenin signaling pathway

作　　者：聂伟东 贾默然[1] 邵轶群 盛东亚 彭煜[1] NIE Weidong;JIA Moran;SHAO Yiqun;SHENG Dongya;PENG Yu(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437

出　　处：《现代肿瘤医学》2024年第4期589-595,共7页Journal of Modern Oncology

基　　金：国家自然科学基金项目(编号:82104720)。

摘　　要：目的:探讨仙鹤草内酯(agrimonolide,AM)对前列腺癌细胞增殖和侵袭的影响及其作用机制。方法:采用细胞计数试剂盒(cell counting kit-8,CCK8)和细胞克隆形成实验检测仙鹤草内酯对前列腺癌细胞增殖的影响;利用流式细胞术检测仙鹤草内酯对前列腺癌细胞凋亡的影响;Transwell实验检测仙鹤草内酯对前列腺癌细胞侵袭的影响;蛋白免疫印迹法(Western blot)检测仙鹤草内酯对前列腺癌细胞中Wnt/β-连环蛋白(β-catenin)信号通路中相关蛋白表达水平的影响;使用慢病毒感染技术稳健过表达β-catenin DU145细胞株。结果:与空白对照组相比,随着仙鹤草内酯药物浓度增加,前列腺癌细胞(DU145、PC-3)活力逐渐降低,其半数抑制浓度(IC50)分别为20.33μmol/L、21.05μmol/L。与空白对照组相比,仙鹤草内酯显著抑制前列腺癌细胞克隆形成、促进细胞凋亡,效果呈剂量依赖性。仙鹤草内酯组显著抑制Wnt/β-catenin信号通路相关蛋白β-catenin,磷酸化葡萄糖合成激酶3β抗体(phospho-glycogen synthase kinase 3 beta,p-GSK3β)/糖原合酶激酶3β(GSK3β),c-Myc癌基因(c-Myc)和G1/S-特异性周期蛋白-D1(Cyclin D1)的表达,且呈浓度依赖性。在过表达β-catenin的DU145细胞株中,仙鹤草内酯的抑制肿瘤增殖和抗转移能力明显减弱。结论:仙鹤草内酯可通过抑制Wnt/β-catenin信号通路诱导细胞凋亡来抑制前列腺癌细胞增殖和侵袭。Objective:To investigate the effects of agrimonolide(AM)on proliferation and invasion of prostate cancer cells,and its mechanism of action.Methods:The cell counting kit-8(CCK8)assay and colony formation assay were used to assess the influence of AM on cell proliferation.Flow cytometry was employed to examine the impact of AM on apoptosis of prostate cancer cells.The Transwell assay was conducted to evaluate the effect of AM on cell invasion.Western blot analysis was employed to investigate the effects of AM on proteins related to the Wnt/β-catenin signaling pathway in prostate cancer cells.Additionally,the DU145 cell line overexpressing β-catenin was established using lentiviral infection technology.Results:Compared with the control group,AM treatment led to a gradual decrease in cell viability of prostate cancer cells,with respective IC 50 of values 20.33μmol/L,21.05μmol/L.AM significantly inhibited colony formation of prostate cancer cells in a concentration-dependent manner.AM treatment resulted in a significant increase in apoptosis rate of prostate cancer cells compared with the control group,showing a concentration-dependent effect.AM treatment markedly suppressed the expression of Wnt/β-catenin signaling pathway related proteinβ-catenin,p-GSK3β/GSK3β,c-Myc and Cyclin D1 in prostate cancer cells compared with the control group.In the DU145 cell line overexpressing β-catenin,the inhibitory effects of AM on tumor proliferation and metastasis were significantly attenuated.Conclusion:AM can inhibit the proliferation and invasion of prostate cancer cells by inducing cell apoptosis through the suppression of the Wnt/β-catenin signaling pathway.

关 键 词：仙鹤草内酯 前列腺癌 增殖 凋亡 侵袭 WNT/Β-CATENIN信号通路 

分 类 号：R737.25[医药卫生—肿瘤]