Ursolic acid ameliorates azoxymethane/dextran sulfate sodium-caused colorectal cancer by inhibition of Wnt signaling cascade  

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

机构地区：[1]State Key Laboratory of Southwestern Chinese Medicine Resources,Department of Pharmacology,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Institute of Chinese Medical Sciences,University of Macao,Macao,China

出　　处：《中国药理学与毒理学杂志》2021年第10期780-781,共2页Chinese Journal of Pharmacology and Toxicology

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);Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。

摘　　要：OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and pro

关 键 词：ursolic acid colitis associated cancer Wnt/β-catenin signaling pathway 

分 类 号：R285[医药卫生—中药学]