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Study Of The Mechanism Of Recombinant Polypeptide Of Fibronectin CH50 Improvement Of Positive Immune Regulatory Effect Of Tumor Microenviroment

Posted on:2007-06-04Degree:MasterType:Thesis
Country:ChinaCandidate:J Y XiangFull Text:PDF
GTID:2144360242463132Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Objective: To investigate the inhibition of tumor by the in vivo expression of recombinant polypeptide of fibronectin CH50 after non-targeting transfection, and the effect of CH50 on T cells and immune regulatory molecules in tumor environment. Methods: Mice inoculated with H22 hepatocarcinoma cells were treated by in vivo transfection of expressoin vector of CH50, which was performed by the hydrodynamics-based gene delivery technique. The control groups were given control plasmid and normal saline respectively. The expression of genes of B7-1, B7-H1, B7-DC, IL-10, TGF-βin the local tumor tissues was detected by semi-quantitative RT-PCR, gel imaging and analysis system at different times in the process of tumor therapy. The quantity of T lymphocytes in the local tumor was analyzed by flow cytometry. Results: The growth of tumor was significantly suppressed by the treatment with non-targeting transfection of CH50 expression vector in vivo. The expression of gene of B7-1, B7-H1, B7-DC, IL-10 and TGF-βwas up-regulated along with the growth of tumor. The treatment with CH50 augmented the up-regulation of the expression of B7-1, B7-H1 and B7-DC genes. The ratios of B7-1/B7-H1 and B7-1/B7-DC in the treated group were significantly higher than those in control groups. The treatment with CH50 produced significantly inhibitory effect on the up-regulation of the expression of IL-10 and TGF-βgenes. The direct action of CH50 on H22 cells resulted in the down-regulatoin of TGF-βgene. The quantity of T lymphocytes in tumor tissues of CH50-treatment group was significantly higher than that in both control groups. Conclusion: The expression of polypeptide CH50 by non-targeting transfection can effectively inhibit the growth of tumor in vivo. The regulation on the immunoregulatory genes in tumor microenvironment and improvement of positive regulatory effect are important part of the mechanism of treatment with CH50.
Keywords/Search Tags:immune regulation, costimulatory molecules, cytokines, hepatocarcinoma
PDF Full Text Request
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