Journal Article

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

Gao, Hengjun, Zhang, Jiao, Xu, Lin, Tian, Yanan, Wang, Jianping, Zhang, Kai, Shen, Huimin, Sun, Xiaoyan, Sun, Qi, Zhao, Qiujie, Sun, Fengkai, Li, Fanni, Liu, Jun

2019

Overview

Background Interleukin-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. Methods The 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. Results IL-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. Conclusions Our 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.

• Publisher: BioMed Central,BMC
• Subject: Apoptosis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Cell Line, Tumor / Cell Movement / Gene Expression Regulation, Neoplastic / Hep G2 Cells / Hepatocellular carcinoma / Humans / Immunology / Integrin beta3 - genetics / Integrin beta3 - metabolism / Integrin αvβ3 / Integrins - genetics / Integrins - metabolism / Interleukin-8 / Interleukin-8 - genetics / Interleukin-8 - metabolism / Invasion / Liver Neoplasms - genetics / Liver Neoplasms - metabolism / Neoplasm Metastasis / Oncology / Phosphatidylinositol 3-Kinases - metabolism / Proto-Oncogene Proteins c-akt - metabolism / Signal Transduction / Up-Regulation