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The Effect of Anti-Hepatocellular Carcinoma of HSV-tk Gene Therapy Mediated by Cationic Liposome in vitro and in vivo
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Abstract:
In order to investigate the effect of anti-hepato-cellular carcinoma of HSV-tk suicide gene system, we constructed the HSV - tk recombinant retroviral vector pLXT. SMMC - 7721 hepatocellular carconoma cells more transfected with pLXT by lipofectin were obtained by subsequent G418 screen. 3H-TdR incorparation assay showed that HSV - tk/ACV had strong cytotoxic effect on HSV - tk gene transfected tumor cells. Lipofectin pLXT complex was directly injected into murine H22 hepatoma tissue, followed by delivery of ACV prodrup, and it was found that the tumor growth masses more greatly reduced. Animals treated with Liptk ACV and tk ACV had an apparent reduction of tumor size as compared with the animals in other six groups ( P < 0.001, P < 0.05). In addition, there was a significant reduction of tumor size between animals treated with Liptk ACV and tk ACV ( P < 0.02). No significant difference was observed in terms of growth rate of tumors among other six control groups. These results indicate the approach that the recombinant retroviral vector was transduced by cationic liposome is simple, safe and efficient, and could make HSV - tk gene acquire persistence of expression in HCC cells. HSV - tk/ACV system showed strong cytotoxic effect, which suggested to has a strong bystander effect in vivo. In addition, it is efficient that nude HSV-tk gene is directly injected into hepatocellular carcinoma tissue.
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