鹅脱氧胆酸及其衍生物在肝胆肿瘤中的作用机制

祁飞; 唐映梅

doi:10.3969/j.issn.1001-5256.2018.05.041

鹅脱氧胆酸及其衍生物在肝胆肿瘤中的作用机制

DOI: 10.3969/j.issn.1001-5256.2018.05.041

祁飞,
唐映梅

昆明医科大学第二附属医院消化内科

基金项目:

云南省卫生科技计划项目(2014NS109、2017NS280)；昆明医科大学研究生创新基金(2017S103)；

详细信息

中图分类号: R735.7;R735.8
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出版历程
- 出版日期: 2018-05-20

The mechanism of chenodeoxycholic acid and its derivatives in hepatobiliary tumor

The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China

Research funding:

摘要

摘要:
鹅脱氧胆酸(CDCA)是一种初级胆汁酸,参与肝胆系统营养物质的消化、转运、吸收过程;法尼醇X受体(FXR)是核受体超家族的一员,体内外研究证实CDCA为FXR的最适配体,可在体内参与多种细胞信号传导通路,抑制肝胆肿瘤细胞的增殖并诱导其凋亡。综述了CDCA与肝胆肿瘤的相关性。
- 肝肿瘤 /
- 胆道肿瘤 /
- 鹅脱氧胆酸 /
- 综述
Abstract:
Chenodeoxycholic acid ( CDCA) is a primary bile acid and is involved in the digestion, transportation, and absorption of nutriments in the hepatobiliary system. Farnesoid X receptor ( FXR) is a member of the nuclear receptor superfamily. In vivo and in vitro studies have demonstrated that CDCA is the natural ligand for FXR and involved in many cell signaling pathways, and it can inhibit the proliferation and induce the apoptosis of hepatobiliary tumor cells. This article reviews the association between CDCA and hepatobiliary tumor.
- liver neoplasms /
- biliary tract neoplasms /
- chenodeoxycholic acid /
- review

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参考文献(31)

[1]LASKAR MG, ERIKSSON M, RUDLING M, et al.Treatment with the natural FXR agonist chenodeoxycholic acid reduces clearance of plasma LDL whilst decreasing circulating PCSK9, lipoprotein (a) and apolipoprotein C-III[J].J Intern Med, 2017, 281 (6) :575-585.

[2]WANG W, ZHAN M, LI Q, et al.FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHPdependent inhibition of Bcl-x L expression[J].Oncotarget, 2016, 7 (23) :34617-34629.

[3]FORMAN B, GOODE E, CHEN J, et al.Identification of a nuclear receptor that is activated by farnesol metabolites[J].Cell, 1995, 81 (5) :687-693.

[4]ZHANG Y, EDWARDS PA.FXR signaling in metabolic disease[J].FEBS Lett, 2008, 582 (1) :10-18.

[5]FIORUCCI S, CIPRIANI S, MENCARELLI A, et al.Farnesoid X receptor agonist for the treatment of liver and metabolic disorders:focus on 6-ethyl-CDCA[J].Mini Rev Med Chem, 2011, 11 (9) :753-762.

[6]MAKISHIMA M, OKAMOTO A, REPA J.Identification of a nuclear receptor for bile acids[J].Science, 1999, 284 (5418) :1362-1365.

[7]LI Y, JADHAV K, ZHANG Y.Bile acid receptors in non-alcoholic fatty liver disease[J].Biochem Pharmacol, 2013, 86 (11) :1517-1524.

[8]CHEN F, MA L, DAWSON PA, et al.Liver receptor homologue-1 mediates species-and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter[J].J Bio Chem, 2003, 278 (22) :19909-19916.

[9]ZHAO J, LI W, YAO DK.Role of farnesoid X receptor in treatment of primary biliary cholangitis[J].Chin J Dig Dis, 2017, 22 (2) :109-111. (in Chinese) 赵健, 李伟, 姚定康.法尼醇X受体在原发性胆汁性胆管炎治疗中的作用[J].胃肠病学, 2017, 22 (2) :109-111.

[10]XU Q, LI L, WEI WH, et al.Farnesoid X receptor gene polymorphisms and metabolic disese[J].Clin J Clin Pharmacol Ther, 2017, 22 (10) :1180-1188. (in Chinese) 徐千, 李玲, 魏婉慧, 等.法尼酯衍生物X受体基因多态性与代谢性疾病的相关性[J].中国临床药理学与治疗学, 2017, 22 (10) :1180-1188.

[11]MARSCHALLl H, LUKETIC V, LOVGREN-SANDBLOM A.The farnesoid X receptor agonist obeticholic acid increases plasma FGF-19 concentrations and decreases bile acid synthesis in primary biliary cirrhosis[J].J Hepatol, 2012, 56 (2) :s377.

[12]GROBER J, ZAGHINI I, FUJII H, et al.Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene.Involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer[J].J Bio Chem, 1999, 274 (42) :29749-29754.

[13]LEE H, ZHANG Y, LEE FY, et al.FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine[J].J Lipid Res, 2006, 47 (1) :201-214.

[14]LAMBERT G, AMAR MJ, GUO G, et al.The farnesoid X-receptor is an essential regulator of cholesterol homeostasis[J].J Bio Chem, 2003, 278 (4) :2563-2570.

[15]WATANABE M, HOUTEN SM, WANG L, et al.Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c[J].J Clin Invest, 2004, 113 (10) :1408-1418.

[16]HU ZJ, REN LP, WANG C, et al.Protective effect of chenodeoxycholic acid against lipid kidney injury induced by high-fructosefeeding in rats and the underlying mechanism[J].Chin J Nephrol, 2013, 29 (2) :129-136. (in Chinese) 胡志娟, 任路平, 王超, 等.鹅脱氧胆酸对高果糖饮食致大鼠肾损伤的保护作用及其机制[J].中华肾脏病杂志, 2013, 29 (2) :129-136.

[17]FU J, WANG H.Precision diagnosis and treatment of liver cancer in China[J].Cancer Lett, 2018, 412 (1) :283-288.

[18]National Health and Family Planning Commission of the People's Republic of China.Diagnosis, management, and treatment of hepatocellular carcinoma (V2017) [J].J Clin Hepatol, 2017, 33 (8) :1419-1431. (in Chinese) 中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范 (2017年版) [J].临床肝胆病杂志, 2017, 33 (8) :1419-1431.

[19]LI J, QI XS, HAN T, et al.An excerpt of AASLD guidelines for the treatment of hepatocellular carcinoma (2016) [J].J Clin Hepatol, 2017, 33 (4) :621-622. (in Chinese) 李静, 祁兴顺, 韩涛, 等.《2016年美国肝病学会肝细胞癌治疗指南》摘译[J].临床肝胆病杂志, 2017, 33 (4) :621-622.

[20]HAO FJ, CHEN XP.Role of farnesoid X receptor in liver tumor and liver regeneration[J].Acta Med Univ Sci Technol Huazhong, 2013, 42 (3) :369-372. (in Chinese) 郝风杰, 陈孝平.FXR及其在肝脏肿瘤及肝脏再生中的作用[J].华中科技大学学报:医学版, 2013, 42 (3) :369-372.

[21]ZHAO C, CONG YL, XU WJ, et al.Role of farnesoid X receptor in tumor research and treatment[J].Progr Physiolog Sci, 2012, 43 (4) :303-305. (in Chinese) 赵丛, 丛玉玲, 徐纬骏, 等.法尼酯X受体对于肿瘤研究和治疗的作用[J].生理科学进展, 2012, 43 (4) :303-305.

[22]NIE JJ, LI QP, GE XX, et al.Study of bile acid and its receptor in the development of cholangiocarcinoma[J].Natl Med J China, 2016, 96 (10) :830-832. (in Chinese) 聂俊杰, 李全朋, 葛贤秀, 等.胆汁酸及其受体在胆管癌发生发展过程中的研究进展[J].中华医学杂志, 2016, 96 (10) :830-832.

[23]DAI J, WANG H, SHI Y, et al.Impact of bile acids on the growth of human cholangiocarcinoma via FXR[J].J Hematol Oncol, 2011, 4:41.

[24]WANG W, YIN X, LI G, et al.Expressions of farnesoid X receptor and myeloid cell leukemia sequence 1 protein are associated with poor prognosis in patients with gallbladder cancer[J].J Chin Med Assoc, 2014, 127 (14) :2637-2642.

[25]DAI J, WANG H, DONG Y, et al.Bile acids affect the growth of human cholangiocarcinoma via NF-κB pathway[J].J Cancer Invest, 2013, 31 (2) :111-120.

[26]ZHANG Y, HAGEDORN CH, WANG L.Role of nuclear receptor SHP in metabolism and cancer[J].J Biochim Biophys Acta, 2011, 1812 (8) :893-908.

[27]QIN CY, LIU H.Apoptosis-inducing effect of synthetic chenodeoxycholic acid derivative, HS 1200, in human hepatoma cell line BEL-7402 and the mechanisms involved[J].World Chin J Dig, 2010, 18 (7) :641-645. (in Chinese) 秦成勇, 刘慧.鹅脱氧胆酸衍生物HS-1200诱导人肝癌细胞株凋亡的作用及机制[J].世界华人消化杂志, 2010, 18 (7) :641-645.

[28]ZHANG ZH, LIU WQ, LAI YS.Advances in research on antitumor effect of bile acid derivatives[J].Progr Pharm Sci, 2010, 34 (11) :491-498. (in Chinese) 张之昊, 刘文清, 赖宜生.胆汁酸衍生物的抗肿瘤作用研究进展[J].药学进展, 2010, 34 (11) :491-498.

[29]YEE SB, SONG YS, JEONG SH, et al.A novel chenodeoxycholic derivative HS-1200 enhances radiation-induced apoptosis in MCF-7 cells[J].Oncol Rep, 2007, 17 (4) :919-923.

[30]PARK SE, LEE SW, HOSSAIN MA, et al.A chenodeoxycholic derivative, HS-1200, induces apoptosis and cell cycle modulation via Egr-1 gene expression control on human hepatoma cells[J].Cancer Lett, 2008, 270 (1) :77-86.

[31]LIU H, QIN CK, HAN GQ, et al.Synthetic chenodeoxycholic acid derivative, HS-1200, induces apoptosis of human hepatoma cells via a mitochondrial pathway[J].Cancer Lett, 2008, 270 (2) :242-249.

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