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Anti-Tumor Study of pOSP1-HSVtk Gene Therapy by Polyethylenimine Mediated Transfection in Ovarian Cancer
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Abstract:
Objective: To study the anti-tumor effects of suicide gene therapy using an ovarian-specific promoter and polyethylenimine(PEI) mediated transfection. Methods : (1) The pOSP1-HSVtk plasmids containing an ovarian-specific promoter were transfected using PEI into the Human ovarian carcinoma cell SKOV3, Human lung carcinoma cell NCI-H460 and Human heptocellular carcinoma cell HepG2. The cytotoxicities resulted from GCV were evaluated using the MTT assay. (2) Ovarian cancer xenograft model was established and the PEI/ pOSP1-HSVtk complex were injected around the xenograft. The expressed TK activities were estimated by monitoring the GCV concentration change using a HPLC assay. The weight of the nude mice, the tumor volumes and tumor weights were all recorded to calculate the tumor inhibition rates by weight and by volume. Histopathological analysis and TUNEL method were also performed. Results : (1) GCV was shown to be toxicity only in SKOV3 cells. (2) Compared with the control group, GCV concentrations in tumor tissues transfected pOSP1-HSVtk were shown to be significantly lower (0.05>P>0.01). The tumor volume and the tumor weight were also significantly decreased in the treated group(P<0.01). The tumor volume inhibition rate and the tumor weight inhibition rate were estimated to be 63.66% and 58.98% respectively. Histological examination revealed heavy haemorrhage and necrosis in the tumor tissues, and TUNEL confirmed substantial cell apoptosis in the treated group. Conclusion: The suicide gene therapy system using an ovarian-specific promoter by polyethylenimine mediated transfection has a targeting killing activity on human ovarian cancer.
Keywords:
polyethylenimine ; suicide gene ; ovarian cancer ; gene therapy
