Impact of bile acids on the growth of human cholangiocarcinoma via FXR.
Impact of bile acids on the growth of human cholangiocarcinoma via FXR.
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DOI：
10.1186/1756-8722-4-41
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发表时间：
2011-10-12
影响因子：
28.5
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Dai J;Wang H;Shi Y;Dong Y;Zhang Y;Wang J
本研究旨在探讨不同类型胆汁酸对胆管癌增殖的影响及其可能的分子机制。采用PCR法和Western blot法检测farnesoid x受体（FXR） mRNA和蛋白水平的表达。采用免疫组化方法检测26例患者和10例正常人胆管癌组织中FXR的表达。并在裸鼠模型上研究了其对体内肿瘤生长的影响。游离胆汁酸诱导FXR表达增加；与此相反，共轭胆汁酸降低了FXR的表达。用FXR激动剂GW4064和FXR拮抗剂GS说明了FXR的作用。更具体地说，当游离胆汁酸与FXR激动剂GW4064联合使用时，肿瘤细胞抑制作用更加明显。但加入FXR拮抗剂GS后，游离胆汁酸对肿瘤的抑制作用减弱。GS与CDCA联合处理可逆转CDCA对FXR表达的调节作用。CDCA和GW 4064可显著抑制肿瘤生长。CDCA + GW 4064联合组的抑制作用更为明显。同样，结合胆汁酸- gdca促进肿瘤生长。我们还发现FXR激动剂GW4064能有效阻断GDCA对肿瘤生长的刺激作用。FXR在小鼠胆管癌组织中的表达特点及差异与前期实验结果一致。胆管癌患者正常组织与肿瘤组织中FXR的表达也有显著差异。游离胆汁酸与结合胆汁酸的比例失衡可能在胆管癌的发生中起重要作用。FXR是核受体超家族的一员，可能介导胆汁酸诱导的作用。
The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms. PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR) in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumor growth were also studied in nude mouse model. Free bile acids induced an increased expression of FXR; on the contrary, the conjugated bile acids decreased the expression of FXR. The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. But adding FXR antagonist GS into the treatment attenuated the tumor inhibitory effect caused by free bile acids. Combined treatment of GS and CDCA could reverse the regulating effect of CDCA on the expression of FXR. Administration of CDCA and GW 4064 resulted in a significant inhibition of tumor growth. The inhibitory effect in combination group (CDCA plus GW 4064) was even more pronounced. Again, the conjugated bile acid-GDCA promoted the growth of tumor. We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. And the characteristic and difference of FXR expressions were in agreement with previous experimental results in mouse cholangiocarcinoma tissues. There was also significant difference in FXR expression between normal and tumor tissues from patients with cholangiocarcinoma. The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the effects induced by the bile acids.
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影响因子：
2.7
作者：
Schramm G;Surmann EM;Wiesberg S;Oswald M;Reinelt G;Eils R;König R
通讯作者：
König R
影响因子：
13.5
作者：
Wang, Yan-Dong;Chen, Wei-Dong;Wang, Meihua;Yu, Donna;Forman, Barry M.;Huang, Wendong
通讯作者：
Huang, Wendong
影响因子：
11.2
作者：
Swales, Karen E.;Korbonits, Marta;Bishop-Bailey, David
通讯作者：
Bishop-Bailey, David
影响因子：
4.8
作者：
Huang, L;Zhao, A;Cui, JS
通讯作者：
Cui, JS
影响因子：
8
作者：
Debruyne, PR;Bruyneel, EA;Mareel, MM
通讯作者：
Mareel, MM