Sodium Cantharidina And SiRNA Influence The S100A3Expression In Heptocellar Carcinoma And Its Function

Telepathically carcinoma (HCC) is the second and the third tumor associateddeath cause in China and worldwide, respectively. Although the surgery and livertransplantation provided valid approaches for HCC, the5-years recurrence rate arealways up to54.1-61.5%, of which62.4-77.8%occurred in the first two years afterresections and it will lead to the poorer prognosis.The S100protein family comprises22members whose protein sequencesencompass at least one EF-hand Ca2+binding motif. S100proteins are localized inthe cytoplasm and/or nucleus of a wide range of cells, and involved in the regulationof a number of cellular processes such as cell cycle progression and differentiation.Seventeen S100s family members are located as a cluster on chromosome1q21-22, aregion frequently rearranged in several tumors. In addition, molecular analysis hasrevealed that several S100s, including S100A2, S100A4, S100A7and S100A10,exhibit altered expression levels in hepatocellular carcinoma. So it is interesting tosystematically investigate the expression of other members of S100family inhepatocellular carcinoma and normal liver tissues.Patients who were experienced hepetectomy due to HCC from Mar,2011to Mar,2013in the Second Affiliated Hospital of Jilin University were chosen for this project.The clinical surgical specimens, including HCC tissues, tumor-surrounding tissuesand normal liver tissues, were gathered. The clinical characters including age, gender,original tumor size, infection of HBV, serum level of AFP, portal vein tumor embolus,degree of differentiation, metastasis and clinicopathologic stage were used to furtheranalysis with the experimental results. To investigate the expression level of S100A3among human hepatocellular carcinoma (HCC) tissues, the adjacent tumor tissues andnormal hepatic tissues by means of immunohistochemical stain and RT-PCR.In vitro experiments, we have studied the effect of cantharidin sodium on theexpression of S100A3in the hepatocellular carcinoma cell lines HepG2and Huh7respectively. The function of candidature sodium on inducing hepatocellularcarcinoma cell apoptosis has also been investigated. Finally, the effects of RNAinterference on S100A3protein and mRNA in HepG2cell was also studied. Thetumorgenicity and lethal ability of HepG2cell in NSG mice model was studied. The results have showed that S100A3protein and mRNA expression level ishigher in HCC tissues than that in adjacent tissues and normal hepatic tissue. Thepositive staining rate of S100A3protein in HCC tissues is significantly higher thanthat in para-cancer tissues and normal liver tissues.The expression rate of S100A3protein in HCC tissues is positive correlation with the degree of tumor celldifferentiation.Candidature sodium has a potent function of inducing hepatocellular carcinomacell lines HepG2and Huh7apoptosis. The gene and protein level of in cell wassignificantly negative correlation with apoptosis: S100A3level in cells becomes lowrefer that cell death. S100A3siRNA can decrease the gene and protein level ofS100A3in HepG2cell lines. The tumorgenicity functon of HepG2cell damagedseriously by S100A3siRNA inducing that mice get long survival.All in all, We have found that S100A3protein and mRNA expression level ishigher in HCC tissues than that in adjacent tissues and normal hepatic tissue. Theexpression rate of S100A3protein in HCC tissues is positive correlation with thedegree of tumor cell differentiation. Candidature sodium has a potent function ofinducing hepatocellular carcinoma cell lines HepG2and Huh7apoptosis in vitro.S100A3siRNA can decrease the gene and protein level of S100A3in HepG2cellproceeding to influence the tumorgenicity and lethal ability in mouse model. Thisstudy will provide new directions and methods for drug and gene therapy ofhepatocellular carcinoma.