Mitf silencing cooperates with IL-12 gene transfer to inhibit melanoma in mice.
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.
Nakai
Noriaki
N
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan.
Kishida
Tsunao
T
Hartmann
Gunther
G
Katoh
Norito
N
Imanishi
Jiro
J
Kishimoto
Saburo
S
Mazda
Osam
O
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
D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D004247:DNA