Abstract
CXCL8, a member of CXC chemokines, was constitutively expressed in many types of human cancers, and its overexpression has been shown to play a critical role in promoting tumorigenesis. The purpose of the present study was to determine CXCL8 expression in a commercial human liver tissue microarray, and elucidate the effects and underlying mechanisms by which CXCL8 is involved in the malignant progression of human liver cancer. Our data showed that high level expression of CXCL8 in tissues with liver cancer was identified as compared with non-cancer tissues, and its up-regulation was closely associated with clinical stage and tumor infiltration. In vitro, exogenous CXCL8 at concentrations of 10, 20 or 40 ng/ml obviously stimulated the proliferation abilities of HepG2 cells. Coupled with this, 10, 20 or 40 ng/ml of exogenous CXCL8 also triggered a significant elevation in HepG2 cells migration. Additionally, overexpression of CXCL8 in HepG2 cells also resulted in increased cell proliferation and migration capacities. Finally, Western blotting analysis showed that overexpression of CXCL8 increased the expression of ERK, p-ERK and survivin, decreased the expression of caspase-3 and BAX at protein level.
Highlights
Liver cancer, the predominant primary malignancy, ranks as the fifth most commonly diagnosed cancer in male and the seventh in female around the world [1]
The results from immunohistochemistry assay showed that the expression of CXCL8 at protein level was markedly increased in liver cancer tissues (Figure 1A–C), whereas normal liver tissue showed a decreased expression of CXCL8 protein (Figure 1D) (P=0.0246)
Statistical analysis form liver cancer tissues demonstrated that up-regulated level of CXCL8 was positively concerned with high clinical stage and tumor infiltration (P=0.0061)
Summary
The predominant primary malignancy, ranks as the fifth most commonly diagnosed cancer in male and the seventh in female around the world [1]. Of the two infection diseases, HBV is suggested to be implicated in 75–80% of virus-associated liver cancer, while HCV is implicated in 10–20%, suggesting a predominant role of inflammation/immune response in the process of liver cancer [6]. Chemokines, named as chemoattractant cytokines, are a large subfamily of small heparin-binding proteins and originally characterized by their properties to direct and recruit the movement of various leukocyte subsets [7]. On the basis of the position of the cysteine residues adjacent to the N-terminal, chemokines were classified into four conserved subfamilies (namely CC, CXC, CX3C and C), and they
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