The mechanism of pseudomonasaeruginosa mannose sensitive hamemagglutination vaccine in inducing apoptosis of hepatocellular carcinoma / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the mechanism of pseudomonasaeruginosa mannose sensitive hamemagglutination vaccine (PA-MSHA) in inducing apoptosis in hepatocellular carcinoma (HCC).MethodsA metastatic model of human hepatocellular carcinoma (HCC) was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were randomly divided into three groupscontrol group,PA-MSHA intraperitoneal administration group,and PA-MSHA subcutaneous administration group.The agent was administered every day after the third day post-tumor implantation.At the end of the sixth week,the mice were killed.Serum levels of TNF-α,IL-4,IL-6 and IFN-γ were measured by ELISA and the activities of caspase 3,caspase 8 and caspase 9 in the tumor samples were tested by spectrophotometric method.Fas/FasL expressions were evaluated by Western blotting.ResultsSerum TNF-α levels in the control group,PA-MSHA subcutaneous administration group and PA-MSHA intraperitoneal administration group were 25.24±3.22 pg/ml,25.50±4.55 pg/ml(P＞0.05) and 34.22±2.42 pg/ml (P＜0.01),respectively,while there were no significant differences in serum IL-4,IL-6 and IFN-γ among these three groups(P＞0.01).Compared with the control group,the activities of caspase 3,caspase 8 and caspase 9 in tumors in the intraperitoneal administration group increased by 4.1,2.3 and 1.9 fold(P＜0.01),respectively,and Fas/FasL expressions were significantly elevated in the intraperitoneal administration group and subcutaneous administration group.ConclusionWhen given intraperitoneally,PA-MSHA can induce apoptosis in HCC by promoting the secretion of TNF-α and expression of Fas/FasL,thereby inhibiting HCC growth and metastasis.