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

Anticancer Res. 2001 Jul-Aug;21(4A):2537-45.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Division / drug effects
  • Cell Division / genetics
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / physiology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Genes, p16*
  • Genetic Vectors / genetics
  • Humans
  • Microtubule-Associated Proteins / biosynthesis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • Transduction, Genetic*
  • Tumor Cells, Cultured
  • Vindesine / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclin-Dependent Kinase Inhibitor p16
  • Microtubule-Associated Proteins
  • Paclitaxel
  • Vindesine