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.
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 humanovarian cancer cell lines, SKOV-3 and OVCAR-5, were used in this study. We transduced the full-length humanp16 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.
Authors: BreeAnn N Brandhagen; Chelsea R Tieszen; Tara M Ulmer; Maria S Tracy; Alicia A Goyeneche; Carlos M Telleria Journal: BMC Cancer Date: 2013-01-26 Impact factor: 4.430