Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference

H. Sumimoto, S. Yamagata, A. Shimizu, H. Miyoshi, H. Mizuguchi, T. Hayakawa, M. Miyagishi, K. Taira, Y. Kawakami

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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.

Original languageEnglish
Pages (from-to)95-100
Number of pages6
JournalGene Therapy
Volume12
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

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Keywords

  • Adenovirus
  • Lentivirus
  • RNA interference
  • Skp-2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Sumimoto, H., Yamagata, S., Shimizu, A., Miyoshi, H., Mizuguchi, H., Hayakawa, T., Miyagishi, M., Taira, K., & Kawakami, Y. (2005). Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference. Gene Therapy, 12(1), 95-100. https://doi.org/10.1038/sj.gt.3302391