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.
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Acknowledgements
We thank Dr M Matsuoka for his helpful discussion and critical review of our manuscript. This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant-in-aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, for Second Term Comprehensive 10-year Strategy for Cancer Control, the Science Research Promotion Fund from the Promotion and Mutual Aid Cooperation for Private Schools for Japan, and the Keio Gijuku Academic Development Funds.
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Sumimoto, H., Yamagata, S., Shimizu, A. et al. Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference. Gene Ther 12, 95–100 (2005). https://doi.org/10.1038/sj.gt.3302391
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DOI: https://doi.org/10.1038/sj.gt.3302391
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