淫羊藿素通过阻断Notch信号通路抑制肝癌增殖  

Icaritin Inhibits Cellular Proliferation Hepatocellular Carcinoma through Blockade of Notch Signaling Pathway

作　　者：李月 李玉瑶 冯海 余卓[1] 高月求[1] LI Yue;LI Yuyao;FENG Hai;YU Zhuo;GAO Yueqiu(Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203

出　　处：《中华中医药学刊》2023年第11期134-137,I0031,I0032,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81774240,82074154);国家自然科学基金项目(81874436)。

摘　　要：目的通过体外和体内实验,评价淫羊藿素对肝癌细胞和肿瘤小鼠模型的治疗作用,探讨淫羊藿素抑制肝癌增殖的作用机制。方法采用H22小鼠肝癌细胞株作为实验对象,应用CCK-8法检测不同浓度的淫羊藿素对肿瘤细胞增殖的影响。使用半数抑制浓度(IC50)的淫羊藿素作用于肿瘤细胞,通过western blot方法检测细胞中Notch信号通路受体Notch1、Notch2、Notch3的表达。使用BABL/C小鼠构建肝癌原位移植模型。模型小鼠随机分为对照组(生理盐水组)和治疗组(淫羊藿素组),治疗后观察和记录小鼠的体征变化以及生存时间。采用同样方法构建小鼠模型,治疗20 d后处死,收集肝脏和肿瘤组织,检测肝脏和肿瘤质量;通过免疫组化染色法,检测肝脏组织中肿瘤细胞增殖状况;应用western blot方法检测肿瘤组织内Notch信号通路受体表达情况。结果体外实验中,淫羊藿素阻断Notch信号通路受体表达,显著抑制肿瘤细胞增殖。体内实验中,淫羊藿素阻断Notch信号通路表达,显著抑制肿瘤生长,延长荷瘤小鼠的生存时间。结论淫羊藿素通过阻断Notch信号通路,抑制肝癌细胞体外和体内的增殖和生长,延长小鼠的生存时间。Objective This study is to investigate the therapeutic effect of icaritin on hepatocellular carcinoma(HCC)and HCC mouse models in vitro and in vivo,exploring the mechanism of icaritin on inhibiting the proliferation of HCC.Methods HCC cell line H22 of the mice was used in this study.CCK-8 assay was performed to detect the effect of icaritin in various concentrations on the proliferation of HCC cells.The half-inhibitory-effect concentration(IC_(50))of icaritin was used to treat HCC cells,and the expressions of the receptors in Notch signaling pathway,including Notch1,Notch2 and Notch3,were examined in HCC cells.BABL/C mice were used to construct in situ orthotopic HCC models,and they were randomized into saline-treated group named as the control group and the icaritin-treated group named as the treatment.The body indicator and survival time were monitored in mice models after the treatment.In another experiment,the mice were euthanized 20 days after treatment,and the liver tissues were collected.The weights of livers and tumors from different groups were measured,the proliferation of HCC cells was detected in liver tissues by using Ki67 immunostaining,and the expression of the receptors in Notch signaling pathway was assessed in tumor tissues by Wblot.Results In vitro,icaritin effectively blocked the expressions of the receptors in Notch signaling pathway,and significantly inhibited cellular proliferation of HCC.In vivo,icaritin significantly abrogated the expression of the Notch signaling pathway,inhibited the tumor growth and prolonged the survival time.Conclusion Icaritin inhibited HCC proliferation in vitro and blocked tumor growth in vivo,extending the survival of mice models.

关 键 词：淫羊藿素 H22 肝癌 NOTCH信号通路 

分 类 号：R285.5[医药卫生—中药学]