Inhibition of colorectal cancer by ursolic acid via noncanonical Hedgehog signaling pathway

作     者：CHEN Li SUN Qiang ZENG Sha ZHAO Hui LIU Mao-lun YANG Han REN Shan MING Tian-qi LU Jin-jian XU Hai-bo CHEN Li;SUN Qiang;ZENG Sha;ZHAO Hui;LIU Mao-lun;YANG Han;REN Shan;MING Tian-qi;LU Jin-jian;XU Hai-bo

作者机构：State Key Laboratory of Southwestern Chinese Medicine ResourcesDepartment of PharmacologyChengdu University of Traditional Chinese MedicineChengdu 611137China Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2021年第35卷第10期

页      面：759-760页

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：National Natural Science Foundation of China(81573813,81173598) Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447) Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917) and Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006) 

主　　题：ursolic acid colorectal cancer noncanonical Hedgehog signaling apoptosis 

摘      要：OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo,and to explore the underlying *** The smoothened(SMO)gene-silenced human colorectal cancer HCT116^(hSMO)cell line was established by transfection with the lentivirus carrying SMO *** cytotoxic effect of ursolic acid on HCT116^(hSMO)cells was determined by MTT *** effect of ursolic acid on the migration of HCT116^(hSMO)cells was studied by wound healing *** effect of ursolic acid on apoptosis of HCT116^(hSMO)cells was explored by Hoechst33342/PI double staining and flow *** effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2,Bax,caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR(RT-qPCR)and Western blotting(WB)***-qPCR and WB were used to examine the relationship between GLI1,c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116^(hSMO)*** effects of ursolic acid on the expressions of GLI1,p-Akt,Akt,c-Myc,SHH and SUFU of noncanonical Hedgehog pathway were evaluated by RT-qPCR and WB *** nude mouse model bearing HCT116^(hSMO)cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in *** body weight and tumor size of mice were assessed regularly every 2 *** effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL *** expressions of Bcl-2,Bax,GLI1,p-Akt,Akt,c-Myc,SHH,SUFU mRNA and proteins were measured by RT-qPCR and *** levels of Bcl-2,Bax,GLI1,p-Akt,c-Myc and SHH proteins in tumor tissues were also evaluated by *** Ursolic acid significantly inhibited the growth and migration of HCT116^(hSMO)cells in vitro,compared with the control(P0.05).Meanwhile,ursolic acid also induced apoptosis of HCT116^(hSMO)cells in vitro(P0.05).Furthermore,SC79(Akt activator)enhanced the expressio