OBJECTIVETo study the anti-tumor effects of combined IL-12 and granalocyte-macrophage-colong scimulating factor (GM-CSF) gene therapy on murine hepatocellular carcinoma.

METHODSTwenty-four mice received subcutaneous inoculation of 1 x 10(6) BNL hepatoma cells were randomly divided into the following four groups with different cytokine encoding plasmids (6 mice for each group): (1)pXX-GM-CSF 12.5 microg and pXX-IL-12 12.5 microg; (2)pXX-IL-12 25 microg; (3)pXX-GM-CSF 25 microg; (4)pXX-Neo 25 microg. The plasmids were given through tail vein using a versatile hydrodynamics-based DNA delivery method on day 3 and day 6 after tumor challenge. The growth of tumor and cellular immune response were observed intensively. The changes in serum concentration of IL-12, GM-CSF, and IFN-gamma after plasmids injection were also observed.

RESULTSCo-delivery of IL-12 and GM-CSF could mount stronger anti-tumor effects, longer term enhanced IL-12 expression and lower level of IFN-gamma than did IL-12 alone.

CONCLUSIONSCombined IL-12 and GM-CSF can render a strong anti-tumor effect as well as a potential to lower the side effects.

Animals ; CD4-Positive T-Lymphocytes ; cytology ; CD8-Positive T-Lymphocytes ; cytology ; Cell Division ; genetics ; physiology ; Genetic Therapy ; methods ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; genetics ; physiology ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; genetics ; physiology ; Liver Neoplasms, Experimental ; genetics ; therapy ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Plasmids ; administration & dosage ; genetics ; Time Factors ; Tumor Cells, Cultured