Antitumor efficacy of naked DNA expressed murine IL-12 in a murine hepatocellular carcinoma model / 中国癌症杂志

ABSTRACT

Purpose: To investigate the antitumor efficacy of intra-tumoral administration of plasmid DNA expressing mIL-12 in murine H22 liver tumor models grafted subcutaneously. Methods: Plasmid encoding mIL12 was constructed and examined the expression of cytokine in the eukaryotic cell through enzyme-linked immunosorbent assay (ELISA). The proliferation assay of T lymphoblasts was performed for measuring the biological activity of expressed mIL12. After intra-tumoral administration of plasmid DNA, mean diameters of the tumor mass and survival time were measured in each murine models group. Lactic dehydrogenase ( LDH) assay was performed to examine whether or not treatment with different plasmid DNA could induce systemic cytolytic activity of lymphocytes against parental H22 cells. Histopathological analysis was operated after administration of plasmid DNA vectors in each murine model group. Results: Growth of liver tumor was significantly inhibited( F =4. 10, P =0. 03), and activity of CTL against H22 was enhanced in mIL12 gene therapy group as compared with the control group. In the focal treated with pDC511mIL12 plasmid DNA, inflammatory cell infiltration was more extensive and necrosis was more definite than control group at 1 month after DMA injection. Conclusions: Intra-tumoral administration of plasmid DNA encoding interleukin-12 could inhibit the growth of H22 liver tumor and induce the host antitumor immune response efficiently in the murine model.