Plasmid mediated kallistain gene expression via intramuscular electroporation delivery in vivo for treatment of NCI-H446 subcutaneous xenograft tumor

Abstract

Kallistatin (KAL) is a novel anti-tumor protein with anti-angiogenic activity. The aim of this study was to investigate whether intramuscular injection of KAL plasmid DNA by electroporation could inhibit NCI-H446 subcutaneous xenograft tumor growth in mice. The tumor model of BALB/c nude mice was induced by subcutaneous inoculation of 5×106 NCI-H446 cells into the mice right flank. The next day, naked plasmid pEGFP or pKAL was electrotransferred into the skeletal muscle of nude mice (n=6 for each group), with the optimized electroporation conditions. Tumor cells migration were assessed by E-cadherin staining; proliferation was determined by anti-Ki-67 staining; and apoptosis was assayed via TUNEL, tumor microvessel density (MVD) was examined by anti-CD34 staining to evaluate the angiogenesis of tumor. Compared to the pEGFP treating group, tumor growth was inhibited by 85% (pEGFP group: 486±187 mm3 , pKAL group: 71±33 mm3 ) at day 42, the MVD of tumor tissues was significantly decreased, and tumor cellular proliferation was also inhibited. The results indicate that this therapeutic strategy might serve as a promising approach for cancer clinical therapy.