Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and Vinca alkaloids of human ovarian cancer cells.
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.
Kawakami
Y
Y
Department of Clinical Research, National Shikoku Cancer Center, Matsuyama, Ehime, Japan.
Hama
S
S
Hiura
M
M
Nogawa
T
T
Chiba
T
T
Yokoyama
T
T
Takashima
S
S
Tajiri
H
H
Eguchi
K
K
Nagai
N
N
Shigemasa
K
K
Ohama
K
K
Kurisu
K
K
Heike
Y
Y
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*
D000972:Antineoplastic Agents, Phytogenic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008869:Microtubule-Associated Proteins; D017239:Paclitaxel; D014751:Vindesine