title: Mitf silencing cooperates with IL-12 gene transfer to inhibit melanoma in mice.
abstract: Malignant melanoma is a malignant neoplasm originating from the melanocyte lineage. Microphthalmia-associated transcription factor (Mitf) is crucially involved in the melanin synthesis as well as proliferation and survival of melanocyte and melanoma. We previously showed that short interfering RNA (siRNA) that is specific for the Mitf gene (Mitf-siRNA) significantly inhibited growth of B16 melanoma after electro-transfected in vivo into preestablished tumor in mice. Here we assessed efficacy of electroporation-mediated co-transfection of Mitf-siRNA and IL-12 gene in the treatment of murine melanoma. As results, the tumor growth was more strongly inhibited by intratumor co-transfection with Mitf-siRNA and IL-12-encoding plasmid DNA than by transfection with either of the molecules alone. The co-transfection induced intratumor infiltration of CD4+ and CD8+ T cells, and hampered neoangiogenesis in the tumor. The findings suggest that the RNAi/cytokine gene combination therapy by means of electroporation may become a novel and efficacious therapeutic modality to treat neoplasms including melanoma.
authors.affiliation: Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakai
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Norito
authors.initials: N
authors.lastname: Katoh
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: Saburo
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D018274:Electroporation; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000627:therapeutic use; D014162:Transfection
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D004247:DNA