Research Of The Role And Molecular Mechanism Of CXCL2 In Hepatocellular Carcinoma

BackgroundLiver cancer is one of the most common tumors in China,which is the sixth most prevalent cancer and the fourth commonest cause of cancer-induced mortality worldwide.Hepatocellular carcinoma(HCC)is the most commonly primary cancer in liver cancers(comprising 75%-85%of cases).The main reason for the high incidence of HCC in China is mainly due to the high prevalence of HBV infection.Inflaumation has been identified as a new hallmark of cancer.Therefore,it is urgently to study on the mechanisms of inflammatory conditions associated treatment and progression in HCC.Chemokines and its receptors are important components of cancer-related inflammation microenvironment,which affect the cancer progression.C-X-C motif chemokine ligand 2(CXCL2)is a kind of the chemokine,which mainly recruits neutrophils and can promote the growth of some kinds of tumor with combination of CXCR2.However,the role and precise mechanism in HCC is still unknown.So,novel biomarker for diagnosis and treatment are needed in HCC.The main aim of our research is exploring that how CXCL2 regulates progression of HCC.MethodsThe samples of 264 cases of hepatocellular carcinoma tissues and paired peritnloral tissues were collected.We examined the expression level of CXCL2 in these HCC tissues and paired adjacent normal liver tissues by RT-PCR.In addition,we analyze the correlation between the clinicopathological factors and the expression of CXCL2 through SPSS 19.0.Then,overexpressing CXCL2 cell lines were constructed by lentivirus and EdU assay,cck-8 assay and flow cytometry analysis were performed to evaluate the effect of overexpressing CXCL2 in HCC cells proliferation.Furthermore,western blot was used to investigate the molecular variation after overexpressing CXCL2 in HCC.Results:CXCL2 is down-regulated in HCC tissues compared to paired normal liver tissues.High expression of CXCL2 is correlated with the poor prognosis of HCC patients.The CXCL2 high expression group has a significantly higher survival rate than the low expression group(P<0.01).MHCC97H and HCCLM3 were selected for experiments in vitro.The overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis.Moreover,In vivo experiments,CXCL2 overexpression could inhibit tumor growth in nude mice.Conclusion:CXCL2 is downregulated in HCC,and higher expression of CXCL2 indicate better overall survival rate of HCC patients.CXCL2 inhibits the progression of hepatocellular carcinoma through regulating cell apoptosis and cell proliferation.CXCL2 could lead to a novel therapeutic approach of HCC.