Bile acids affect the growth of human cholangiocarcinoma via NF-kB pathway.
We observed that free bile acids (CA, DCA, and CDCA) inhibited the growth of cholangiocarcinoma cells by promoting cell apoptosis, while the conjugated bile acids (GCA, GDCA, and GCDCA) stimulated cell growth. Consistently, we found that GDCA stimulated tumor growth and CDCA decreased tumor growth in xenografted mice. Further, the phosphorylated IkB was downregulated by free bile acids, and was upregulated by the conjugated bile acids. IL-6 and COX-2 were decreased by the free bile acids and increased by the conjugated bile acids. Collectively, these results suggest that the bile acids regulate the growth of cholangiocarcinoma by modulating NF-kB pathway.
Divisions of General Surgery, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiaqi
J
Dai
Hongxia
H
Wang
Ying
Y
Dong
Yinxin
Y
Zhang
Jian
J
Wang
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D001647:Bile Acids and Salts; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D051546:Cyclooxygenase 2