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 | Noriaki Nakai, Tsunao Kishida, Gunther Hartmann, Norito Katoh, Jiro Imanishi, Saburo Kishimoto, Osam Mazda |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 10
Issue 4
Pg. 540-5
(Apr 2010)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 20074674
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright 2010 Elsevier B.V. All rights reserved. |
Chemical References |
- Microphthalmia-Associated Transcription Factor
- RNA, Small Interfering
- Green Fluorescent Proteins
- Interleukin-12
- DNA
|
Topics |
- Animals
- DNA
(genetics)
- Electroporation
- Female
- Gene Silencing
- Gene Transfer Techniques
- Genetic Therapy
- Genetic Vectors
- Green Fluorescent Proteins
(genetics)
- Immunohistochemistry
- Interleukin-12
(genetics)
- Melanoma, Experimental
(genetics, therapy)
- Mice
- Mice, Inbred C57BL
- Microphthalmia-Associated Transcription Factor
(genetics)
- Microscopy, Fluorescence
- Neoplasm Transplantation
- Plasmids
(genetics)
- RNA, Small Interfering
(therapeutic use)
- Transfection
|