Target gene transfer mediated by electroporation for cancer therapy in vivo
A plasmid encoding green florescent protein (GFP) was first used to test efficiency of electroporation and optimize parameters for electroporation in vivo. GFP plasmid was efficiently delivered into muscle by electroporation and robust GFP expression in muscle could be observed more than three weeks. While much less GFP positive cells were observed in tumor and GFP expression could only last 6 days but tumors treated with high voltage/short pulse showed about 2.68 fold more GFP positive cells than tumors treated with low voltage/long pulses. The optimized electroporation parameters was used to mediate therapeutic gene transfer into subcutaneous tumors which derived from T739 mice bladder transitional cell carcinoma cell line (BTT-gfp), human mammary carcinoma cell line (MCF-7) and human hepatoma cell line (SMMC 7721-gfp). Those therapeutic genes included immune reaction regulation factors interleukin12, interleukin2 and GM-CSF or anti-angiogenesis factors such as antisense VEGF121cDNA, soluble form of VEGF receptor (sFlk-1) and Tie2 (ExTek). Inhibition of tumor growth and metastasis were observed in T739 mice carried bladder transitional cell carcinoma and nude mice carried either human breast cancer or liver cancer which were treated with multiple transfers of plasmid encoding interleukine12 mediated by electroporation. MCF-7 and SMMC 7721-gfp derived tumor showed sensitive to single anti-angiogenesis gene therapy, yet definite suppression of growth and metastasis of BTT-gfp tumor was resulted from co-tranfer of sFlk-1 and ExTek gene mediated by electroporation. The results suggest that electroporation is a high efficient, safe and economical method for gene transfer in vivo and electro-gene therapy would be a useful method for solid tumor.
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- Biochemistry & Molecular Biology
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Published In
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Issue
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Related Subject Headings
- Biochemistry & Molecular Biology