Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and vinca alkaloids of human ovarian cancer cells

Y. Kawakami, S. Hama, M. Hiura, T. Nogawa, T. Chiba, T. Yokoyama, S. Takashima, H. Tajiri, K. Eguchi, N. Nagai, K. Shigemasa, K. Ohama, K. Kurisu, Y. Heike

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Abstract

Background: Deletions and point mutations of the p16 gene are detectable in more than 50% of ovarian cancer cells. In this study, we examined the effect of p16 gene transduction on the growth of ovarian cancer cells and on the effect of anti-cancer agents. Materials and Methods: p16-null human ovarian cancer cell lines, SKOV-3 and OVCAR-5, were used in this study. We transduced the full-length human p16 gene using recombinant adenovirus (AxCA-hp16). Results: The spontaneous growth of these cells was significantly inhibited by hp16 transduction. MTT assay revealed that AxCA-hp16 infection induced chemoresistance in both cell lines. Flow cytometric analysis revealed that only hp16-transduced SKOV-3, were arrested at the G1-phase for 3 days whereas those infected with AxCA-mock and OVCAR-5 infected with both recombinant viruses did not. Western blot analysis showed increased microtubule-associated proteins 4 (MAP4) in both cell lines. Conclusion: These results suggest that in SKOV-3 cells, G1-arrest induced by p16-transduction prevents paclitaxel- and vindesine- induced cell death, and in OVCAR-5 cells, the other unknown mechanisms play a role of chemoresistance.

Original languageEnglish
Pages (from-to)2537-2546
Number of pages10
JournalAnticancer research
Volume21
Issue number4 A
Publication statusPublished - 2001 Nov 24

Keywords

  • Chemoresistance
  • Growth inhibition
  • MAP4
  • Ovarian cancer
  • P16

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kawakami, Y., Hama, S., Hiura, M., Nogawa, T., Chiba, T., Yokoyama, T., Takashima, S., Tajiri, H., Eguchi, K., Nagai, N., Shigemasa, K., Ohama, K., Kurisu, K., & Heike, Y. (2001). Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and vinca alkaloids of human ovarian cancer cells. Anticancer research, 21(4 A), 2537-2546.