中国肿瘤生物治疗杂志2024，Vol.31Issue(12)：1204-1210,7.DOI:10.3872/j.issn.1007-385x.2024.12.005
补肾健脾方介导法尼醇X受体抑制肝癌细胞AH-130诱导大鼠恶病质的作用及其机制
Effects of Bushen Jianpi formula on farnesoid X receptor-mediated inhibition of hepatocellular carcinoma AH-130 cell-induced cachexia in rats and its underlying mechanism
摘要
Abstract
Objective:To investigate the effects of Bushen Jianpi formula(BSJP)in mediating the inhibitory effects of farnesoid X receptor(FXR)on cancer cachexia(CC)induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism.Methods:A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells.The rats were divided into five groups:blank control,model control,CDCA(FXR agonist),BSJP,and BSJP+CDCA groups.After modelling,the rats were treated with CDCA,BSJP,or their combination for consecutive 16 days,and their body weights were measured weekly.At the end of the experiment,the rats were sacrificed,and abdominal aortic blood,feces,and brown adipose tissues from the epididymal,inguinal,and scapular regions were collected.Liquid chromatography-mass spectrometry(LC-MS)was used to detect the composition and content of bile acids in serum and feces of rats.WB and qPCR were used to detect the expression of FXR,Wnt family member 10b(Wnt10b),β-catenin,and uncoupling protein 1(UCP-1)in the ileum,brown adipose,and white adipose tissues of rats.Results:Compared with the blank control group,the body mass of the rats in the model group was significantly reduced(P<0.01);compared with the model control group,the body mass of the rats in CDCA,BSJP and BSJP+CDCA groups all increased(P<0.01).Compared with the blank control group,the epididymal,inguinal,scapular,and total brown adipose tissue mass were all elevated in the model control group(all P<0.05);compared with the model control group,the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups(P<0.05),but this decrease was not significant in the scapular region(P>0.05);besides,the total brown fat mass decreased notably in all treatment groups compared to the model control group(all P<0.01).LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups.qPCR and WB results confirmed that,compared to the model group,BSJP and BSJP+CDCA promoted the mRNA and protein expression of FXR in the ileum,brown adipose,and white adipose tissues of rats(all P<0.05),and decreased the mRNA and protein expression of Wnt10b,β-catenin,UCP-1(all P<0.05).Conclusion:The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats,alleviating the associated body weight loss and brown adipose tissue formation.The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b,β-catenin,and UCP-1 in brown adipose tissue through the Wnt signaling pathway.关键词
癌性恶病质/肝细胞癌/补肾健脾方/法尼醇X受体/棕色脂肪Key words
cancer cachexia(CC)/hepatocellular carcinoma/Bushen Jianpi formula(BSJP)/farnesoid X receptor(FXR)/brown adipose tissue分类
医药卫生引用本文复制引用
冯思棋,钟薏,李诗颖,李芸,吴中华,汤晓雯,周张杰,吴婷婷..补肾健脾方介导法尼醇X受体抑制肝癌细胞AH-130诱导大鼠恶病质的作用及其机制[J].中国肿瘤生物治疗杂志,2024,31(12):1204-1210,7.基金项目
2021年度"科技创新行动计划"扬帆计划项目(No.21YF1444400) （No.21YF1444400）
2024年虹口区卫健委中医药科研课题(No.HKZYY-2024-24) （No.HKZYY-2024-24）
虹口区第二轮"国医强优"三年行动计划(2022-2024)(No.HKGYQYXM-2022-10) （2022-2024）
上海市虹口区卫生健康委员会中医药科研课题(No.HKQGYQY-ZYY-2022-17) （No.HKQGYQY-ZYY-2022-17）
2019年上海市中西医结合医院科研课题(No.中西医18-01-02) （No.中西医18-01-02）
上海中医药大学预算内项目(No.2019LK048) （No.2019LK048）
