Adenovirus-mediated p16 gene transfer prevents drug-induced cell death through G1 arrest in human glioma cells

Seiji Hama, Yuji Heike, Ichiro Naruse, Minako Takahashi, Hiroyuki Yoshioka, Kazunori Arita, Kaoru Kurisu, Corey K. Goldman, David T. Curiel, Nagahiro Saijo

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29 Scopus citations


This study examined the effects of full-length p16 gene transfer by recombinant adenovirus on cell growth and on sensitivity to CDDP or ACNU chemotherapies. We developed a recombinant adenovirus expressing the full- length human p16 gene (AxCA-hp16) by the COS-TPC method. AxCA-hp16 was infected into the p16-null human glioma cell line, U251MG. AxCA-hp16 infection inhibited proliferation of U251MG cells. A proliferation assay employing MTT showed that AxCA-hp16 infection induced chemoresistance, preventing CDDP-induced cell death (11- to 15-fold) and ACNU-induced cell death (80- to 92-fold). In the absence of AxCA-hp16, cell death was induced with CDDP or ACNU at 3 to 5 days after treatment, as demonstrated by Trypan- blue exclusion. Flow-cytometric analysis showed that CDDP or ACNU arrested cells in the G2 phase on day 1 and that cells re-entered the cycle on day 3. However, the cells infected with AxCA-hp 16 after CDDP or ACNU treatment showed G 1 arrest on day 5 after re-entering the cycle from G2 arrest on day 3. The cells infected with ÅxCA-hp16 before CDDP or ACNU treatment showed G1 arrest over the 5 days after the infection. This study demonstrated that G1 arrest induced with p16-gene expression prevents ACNU- or CDDP-induced cell death. The cell death induced by ACNU and CDDP therefore appears to occur in the phase after the G1/S check point.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalInternational Journal of Cancer
Issue number1
StatePublished - Jul 3 1998


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