- 作者: Yung-Yu Hsieh, Chien-Heng Shen, Wen-Shih Huang, Chih-Chien Chin, Yi-Hung Kuo, Meng Chiao Hsieh, Hong-Ren Yu, Te-Sheng Chang, Tseng-Hsi Lin, Yung-Wei Chiu, Cheng-Nan Chen, Hsing-Chun Kuo , Shui-Yi Tung
- 作者服務機構: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan R.O.C
- 中文摘要: --
- 英文摘要:
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-kappaB 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-kappaB-DNA-binding activity.
Conclusions:
Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-kappaB may explain a new role of resistin in the link of obesity and gastric cancer. - 中文關鍵字: --
- 英文關鍵字: Gastric cancer, Obesity, TLR4, NF-κB, Resistin