| 胆汁酸及受体TGR5/FXR参与肝细胞癌和胆管细胞癌的发生与发展 |
| 投稿时间：2017-03-13 修订日期：2017-03-22 点此下载全文 |
| 引用本文：林跃军,张楠,聂萌,王林.胆汁酸及受体TGR5/FXR参与肝细胞癌和胆管细胞癌的发生与发展[J].医学研究杂志,2017,46(10):18-21,95 |
| DOI：
10.11969/j.issn.1673-548X.2017.10.006 |
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| 中文摘要:目的 探讨胆汁酸与胆汁酸受体TGR5/FXR在肝细胞癌和胆管癌发生、发展中的作用和可能的机制。方法 通过免疫组化检测胆汁酸受体FXR与TGR5在癌旁组织、肝细胞癌组织和胆管细胞癌组织中的表达水平；采用MTS实验检测不同胆汁酸（石胆酸、鹅脱氧胆酸、牛磺胆酸钠、熊去氧胆酸及胆酸）对人胆管癌细胞系HCCC-9810以及人肝癌细胞系HepG2的增殖凋亡影响；采用流式细胞检测石胆酸和鹅脱氧胆酸对人胆管癌细胞系HCCC-9810和人肝癌细胞系HepG2凋亡的影响。结果 TGR5在肝细胞肝癌和胆管细胞癌组织中呈高表达，与之相反，FXR在肝细胞肝癌和胆管细胞癌中呈现低表达水平；胆汁酸能够促进癌细胞的凋亡，而不同种类的胆汁酸其抑制细胞增殖的效力不同。结论 胆汁酸受体FXR和TGR5参与肝细胞癌和胆管细胞癌的发生、发展；胆汁酸能够抑制HepG2和HCCC-9810增殖与促进HepG2和HCCC-9810凋亡，为研究胆汁酸抗肿瘤作用机制奠定了基础。 |
| 中文关键词:胆汁酸 TGR5受体 FXR受体 肝细胞癌 胆管细胞癌 |
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| Role of Bile Acid and Its Receptors TGR5 and FXR in the Development of Hepatocellular Carcinoma and Cholangiocarcinoma |
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| Abstract:Objective To explore the roles of bile acids (BAs),its nuclear and membrane G-protein-coupled receptors, FXR and TGR5, in the progression of the hepatocellular carcinoma (HCC) and cholangiocarcinoma. Methods We examined the expression of TGR5 and FXR in human hepatocellular carcinoma (HCC), cholangiocarcinoma and the adjacent noncancerous tissues. We investigated the effects of lithocholic acid (LCA), chenodeoxycholic acid (CDCA), taurocholic acid (TLC), ursodesoxycholic acid (UDCA) and cholic acid (CA) on proliferation and apoptosis of cultured HepG2 and HCCC-9810 cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and Annexin V/Propidium Iodide assays. Results Compared with the adjacent noncancerous tissues, the TGR5 levels were higher in the HCC, while the FXR levels were lower in cholangiocarcinoma. Multiple BAs inhibited the proliferation of HepG2 and HCCC-9810 cells and induced apoptosis with different efficacies and in a dose-dependent manner. Conclusion Our findings demonstrate that BAs inhibit proliferation and promote apoptosis of HCC and cholangiocarcinoma cells. Thus, TGR5 and FXR may regulate the initiation and progression of HCC and cholangiocarcinoma similarly as in other cancers. BAs may be developed as potential anti-cancer drugs in future therapy. |
| keywords:Bile acids TGR5 receptor FXR receptor Hepatocellular carcinoma Cholangiocarcinoma |
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