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

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 alpha v beta 3, 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 alpha v beta 3 in HCC and the underlying mechanism of IL-8 and integrin alpha v beta 3 in the invasion of HCC remains unclear. Methods The expression of IL-8, integrin alpha v and integrin beta 3 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 beta 3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8. Results IL-8, integrin alpha v and integrin beta 3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin beta 3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin beta 3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin beta 3 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 beta 3, 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 beta 3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin beta 3 axis may serve as a potential treatment target for patients with HCC.