RRC ID 72921
著者 Hama S, Heike Y, Naruse I, Takahashi M, Yoshioka H, Arita K, Kurisu K, Goldman CK, Curiel DT, Saijo N.
タイトル Adenovirus-mediated p16 gene transfer prevents drug-induced cell death through G1 arrest in human glioma cells.
ジャーナル Int J Cancer
Abstract 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-hp16 after CDDP or ACNU treatment showed G1 arrest on day 5 after re-entering the cycle from G2 arrest on day 3. The cells infected with AxCA-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.
巻・号 77(1)
ページ 47-54
公開日 1998-7-3
DOI 10.1002/(sici)1097-0215(19980703)77:1<47::aid-ijc9>3.0.co;2-#
PII 10.1002/(SICI)1097-0215(19980703)77:1<47::AID-IJC9>3.0.CO;2-#
PMID 9639393
MeSH Adenoviridae Antineoplastic Agents / pharmacology* Cell Death / drug effects Cell Death / genetics Cyclin-Dependent Kinase Inhibitor p16 / genetics* Drug Resistance, Neoplasm / genetics* G1 Phase / genetics Gene Transfer Techniques Genetic Vectors Glioma / genetics* Glioma / pathology* Humans Nimustine / pharmacology* Tumor Cells, Cultured
IF 5.145
リソース情報
ヒト・動物細胞 U-87 MG(RCB0419)