[Antitumoral efficacy by systemic delivery of cationic liposome-plasmid interleukin-15 complexes in murine models of lung metastasis].
2012
AIM: To investigate the therapeutic effect of the plasmid pcDNA3.1-IL15 complexed with cationic liposome(CL-IL15) in the B16-F10 melanoma lung metastasis model.METHODS: A plasmid with high secretive efficiency of IL-15 was constructed and the optimum mix ratio was determined to formulate cationic liposome-plasmid complex with the optimal encapsulation.The CHO-K1 cell line was transfected by CL-IL15.The secretion of transfected IL-15 gene was detected by Western blot and its biological function was measured through the proliferation response of CTLL-2 cytotoxic T cell line of murine by MTT assay.The C57BL/6 mice were inoculated intravenously(i.v.) with B16-F10 melanoma lung metastasis cells then treated(i.v.) by CL-IL15 in a therapeutic setting to derermine the tumorigenesis and research the corresponding mechanisms.RESULTS: The pcDNA3.1-IL15 plasmid was successfully constructed and the mass-ratio of optimal condition of cationic liposome-plasmid with perfect entrapment was 1∶ 5(plasmid: cationic liposome).Western blot analysis displayed the detection of IL-15 both in the medium and the pcDNA3.1-IL15 transfected cells.MTT assay showed that CTLL-2 cells could proliferate with the medium obtained from CHO-K1 cells transfected by CL-IL15.And the administration of CL-IL15 complexes led to the significant inhibition lung metastasis of malignant melanoma(P0.05).CONCLUSION: CL-IL15 could inhibit the metastasis of malignant melanoma and the cationic liposome delivered plasmid pcDNA3.1-IL-15 complexes may be an efficient therapeutic strategy for the treating of lung metastasis.And the effective splenic cell-mediated cytotoxicity and the obvious NK cells recruitment may be involved.
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