title: Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and Vinca alkaloids of human ovarian cancer cells.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Research, National Shikoku Cancer Center, Matsuyama, Ehime, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Hama
authors.forename: M
authors.initials: M
authors.lastname: Hiura
authors.forename: T
authors.initials: T
authors.lastname: Nogawa
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: S
authors.initials: S
authors.lastname: Takashima
authors.forename: H
authors.initials: H
authors.lastname: Tajiri
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: N
authors.initials: N
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Shigemasa
authors.forename: K
authors.initials: K
authors.lastname: Ohama
authors.forename: K
authors.initials: K
authors.lastname: Kurisu
authors.forename: Y
authors.initials: Y
authors.lastname: Heike
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D019942:Genes, p16; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008869:Microtubule-Associated Proteins; D017239:Paclitaxel; D014751:Vindesine