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, Yutaka Kawakami

Research output: Contribution to journalArticle

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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

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Small Cell Lung Carcinoma
RNA Interference
Genetic Therapy
Neoplasms
Cell Cycle
Growth
Lentivirus
Inbred NOD Mouse
HIV-2
SCID Mice
Neoplasm Genes
Adenoviridae
Small Interfering RNA
HIV
Cell Line

Keywords

  • Adenovirus
  • Lentivirus
  • RNA interference
  • Skp-2

ASJC Scopus subject areas

  • Genetics

Cite this

Sumimoto, H., Yamagata, S., Shimizu, A., Miyoshi, H., Mizuguchi, H., Hayakawa, T., ... 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

Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference. / Sumimoto, H.; Yamagata, S.; Shimizu, A.; Miyoshi, H.; Mizuguchi, H.; Hayakawa, T.; Miyagishi, M.; Taira, K.; Kawakami, Yutaka.

In: Gene Therapy, Vol. 12, No. 1, 01.2005, p. 95-100.

Research output: Contribution to journalArticle

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, vol. 12, no. 1, pp. 95-100. https://doi.org/10.1038/sj.gt.3302391
Sumimoto, H. ; Yamagata, S. ; Shimizu, A. ; Miyoshi, H. ; Mizuguchi, H. ; Hayakawa, T. ; Miyagishi, M. ; Taira, K. ; Kawakami, Yutaka. / Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference. In: Gene Therapy. 2005 ; Vol. 12, No. 1. pp. 95-100.
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