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Interleukin-8 promotes integrin β3 upregulation and cell invasion through PI3K/Akt pathway in hepatocellular carcinoma

Authors
  • Sun, Fengkai1
  • Wang, Jianping2
  • Sun, Qi3
  • Li, Fanni4
  • Gao, Hengjun2
  • Xu, Lin1
  • Zhang, Jiao1
  • Sun, Xiaoyan1
  • Tian, Yanan1
  • Zhao, Qiujie1
  • Shen, Huimin1
  • Zhang, Kai1
  • Liu, Jun2
  • 1 Shandong Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, Jingwu Road 324#, Jinan, 250021, China , Jinan (China)
  • 2 Shandong Provincial Hospital Affiliated to Shandong University, Department of Hepatobiliary Surgery, Jinan, Shandong, 250021, China , Jinan (China)
  • 3 The First Affiliated Hospital of Xi’an Jiaotong University, Department of General Surgery, Xi’an, Shaanxi, 710061, China , Xi’an (China)
  • 4 The First Affiliated Hospital of Xi’an Jiaotong University, Department of Talent Highland, Xi’an, Shaanxi, 710061, China , Xi’an (China)
Type
Published Article
Journal
Journal of Experimental & Clinical Cancer Research
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 04, 2019
Volume
38
Issue
1
Identifiers
DOI: 10.1186/s13046-019-1455-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundInterleukin-8 (IL-8) plays a vital role in the invasion and metastasis of hepatocellular carcinoma (HCC), and is closely associated with poor prognosis of HCC patients. Integrin αvβ3, a member of the integrin family, has been reported to be overexpressed in cancer tissues and mediate the invasion and metastasis of HCC cells. However, the relationship between IL-8 and integrin αvβ3 in HCC and the underlying mechanism of IL-8 and integrin αvβ3 in the invasion of HCC remains unclear.MethodsThe expression of IL-8, integrin αv and integrin β3 in HCC cells and tissues was detected by quantitative real-time PCR, Western blot and immunohistochemistry. Transwell assay and Western blot was used to detect the invasiveness, the expression of integrin β3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8.ResultsIL-8, integrin αv and integrin β3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin β3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin β3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin β3 expression was significantly inhibited by transfection with CXCR1 siRNA or CXCR2 siRNA. When we stimulated HCC cells with exogenous IL-8, cell invasion and the levels of integrin β3, p-PI3K, and p-Akt increased, which could be effectively reversed by adding PI3K inhibitor LY294002.ConclusionsOur results suggest that IL-8 promotes integrin β3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin β3 axis may serve as a potential treatment target for patients with HCC.

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