Plasmid mediated kallistain gene expression via intramuscular electroporation delivery in vivo for treatment of NCI-H446 subcutaneous xenograft tumor
Journal Title: Pakistan Journal of Pharmaceutical Sciences - Year 2014, Vol 27, Issue 3
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 electrotransfered into the skeletal muscle of nude mice (n=6 for each group), with the optimized electroporation conditions. Tumor cells migration was 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.
Authors and Affiliations
Dongfang Jia , Chenna Zheng , Jingxian Feng , Jin Zou , Yong Diao
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