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il-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma by inhibiting il-6/stat3 signaling

Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 408-415页

作者： Xing-Yu Pu Dao-Feng Zheng Ai Shen Hai-Tao Gu Xu-Fu Wei Tong Mou Jian-Bo Zhang Rui Liu Department of Medical Imaging Chongqing Medical University Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical University Department of Hepatobiliary Surgery Chongqing Cancer Institute Department of Gastrointestinal Surgery The Second Affiliated Hospital of Chongqing Medical University

Background: Interleukin-37 b(il-37 b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between il-37 b and hepatocellular carcinoma(HCC). The present study aimed to investigate the potential roles of il-37 b in HCC progression. Methods: Subjects( n = 237) were recruited, and serum il-37 b was measured using ELISA. The tumorsuppressive capacity and underlying mechanisms of il-37 b in HCC were investigated in vitro and in vivo. Results: Compared to healthy controls, serum il-37 b levels were elevated in chronic hepatitis B(CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum il-37 b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human il-37 b inhibited proliferation and metastasis in HCC cells. Furthermore, il-37 b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating il-6, pstat3(Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human il-6. Conclusions: il-37 b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating il-6/stat3 signaling. Serum il-37 b may be a biomarker for HBV-HCC and its staging.

关键词： Interleukin-37b Chronic hepatitis B Hepatocellular carcinoma Epithelial-mesenchymal transition il-6/stat3 signaling

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