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- Title
Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference.
- Authors
Sumimoto, H; Yamagata, S; Shimizu, A; Miyoshi, H; Mizuguchi, H; Hayakawa, T; Miyagishi, M; Taira, K; Kawakami, Y
- Abstract
Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.Gene Therapy (2005) 12, 95-100. doi:10.1038/sj.gt.3302391 Published online 23 September 2004
- Subjects
SMALL cell lung cancer; RNA; LENTIVIRUSES; ADENOVIRUSES; HIV; CELLULAR control mechanisms; GENE therapy; THERAPEUTICS
- Publication
Gene Therapy, 2005, Vol 12, Issue 1, p95
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302391