Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells

doi:10.1186/1423-0127-21-59

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/10431

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Title:	Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells
Authors:	Hsieh, Yung-Yu Shen, Chien-Heng Huang, Wen-Shih Chin, Chih-Chien Kuo, Yi-Hung Hsieh, Meng Chiao Yu, Hong-Ren Chang, Te-Sheng Lin, Tseng-Hsi Chiu, Yung-Wei Chen, Cheng-Nan Kuo, Hsing-Chun Tung, Shui-Yi
Contributors:	中山醫學大學
Keywords:	Gastric cancer;Obesity;TLR4;NF-κB;Resistin
Date:	2014-06-14
Issue Date:	2015-03-09T10:33:26Z (UTC)
ISSN:	1021-7770
Abstract:	Background Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Results Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity. Conclusions Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10431 http://dx.doi.org/10.1186/1423-0127-21-59
Relation:	Journal of Biomedical Science 2014, 21:59
Appears in Collections:	[醫學系] 期刊論文

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