片仔癀对大肠癌干细胞自我更新及致瘤能力的抑制作用  

Inhibition of Pien Tze Huang in self-renewal and carcinogenicity of colorectal cancer stem cells

作　　者：魏丽慧 方翌 沈阿灵 陈晓萍 谢秋容 李加鹏 彭军 陈友琴 WEI Li-hui;FANG Yi;SHEN A-ling;CHEN Xiao-ping;XIE Qiu-rong;LI Jia-peng;PENG Jun;CHEN You-qin(Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou 350122,China;Department of Physical Education,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;School of Medicine,Case Western Reserve University,Cleveland 44106,USA)

机构地区：[1]福建中医药大学中西医结合研究院,福州350122 [2]福建省中西医结合老年性疾病重点实验室,福州350122 [3]福建中医药大学体育部,福州350122 [4]美国凯斯西储大学医学院,克利夫兰44106

出　　处：《中华中医药杂志》2022年第1期465-468,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：漳州片仔癀药业股份有限公司横向课题;国家自然科学基金项目(No.81703913,No.81673721);福建省教育厅高校杰出青年科研人才培育计划项目(2018)。

摘　　要：目的:观察片仔癀对大肠癌干细胞自我更新及致瘤能力的影响,并探讨其调控机制。方法:片仔癀干预大肠癌干细胞48 h后,倒置显微镜观察细胞的生长情况,细胞计数仪检测细胞的数量,连续克隆球形成实验检测细胞的自我更新能力,裸鼠移植瘤形成实验观察细胞的致瘤能力,Western Blot检测Lgr-5、c-Myc、β-catenin、SMO和GLI-1的表达。结果:与对照组比较,片仔癀干预后,大肠癌干细胞的数量、自我更新及致瘤能力受到显著抑制(P<0.05),大肠癌干细胞自我更新及致瘤特性调控蛋白Lgr-5和c-Myc表达下调,Wnt/β-catenin信号通路关键调控蛋白β-catenin和Hedgehog信号通路关键调控蛋白SMO和GLI-1的表达均下调。结论:片仔癀具有抑制大肠癌干细胞自我更新及致瘤能力的作用,其机制可能与抑制Lgr-5和c-Myc的表达及Wnt/β-catenin、Hedgehog信号通路的活化有关。Objective:To investigate the effect of Pien Tze Huang(PZH)on the self-renewal and carcinogenicity of colorectal cancer stem cells(CR-CSCs)and explore the underlying mechanism.Methods:CR-CSCs were treated with different concentration of PZH for 48 h,the cell morphology was observed by microscopy and the cell numbers were determined by countstar automated cell counter.Continuous spheroid formation assay was used to detect self-renewal of CR-CSCs.Tumorigenicity assay in nude mice was used to detect the carcinogenicity of CR-CSCs.Western Blot was used to detect the expression of Lgr-5 and c-Myc,as well as the expression ofβ-catenin,SMO and GLI-1.Results:Compared with control group,PZH significantly reduced the cell number,self-renewal and carcinogenicity of CR-CSCs(P<0.05).CR-CSCs self-renewal and tumorigenicity-regulating proteins such as Lgr-5 and c-Myc expression were downregulated.The key regulatory proteinsβ-catenin for Wnt/β-catenin signaling pathway and SMO and GLI-1 for Hedgehog signaling pathway were downregulated.Conclusion:PZH can inhibit the self-renewal and tumorigenic ability of CR-CSCs.The mechanism may be related to inhibite the expression of Lgr-5 and c-Myc and Wnt/β-catenin and Hedgehog signaling pathway activation.

关 键 词：片仔癀 大肠癌干细胞 自我更新 致瘤特性 WNT/Β-CATENIN信号通路 HEDGEHOG信号通路 机制 

分 类 号：R735.34[医药卫生—肿瘤]