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p14ARF upregulation of p53 and enhanced effects of 5-fluorouracil in pancreatic cancer

摘要Objective To investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer.Methods A human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays.Results After transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G1 phase. The proportion of cells in the G1 phase was significantly increased from 58.51% to 75.92 %, and in the S and G2/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48 %, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G2/M phase accumulation, from 11.48% to 53.47 %. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01-10 mg/L) than those devoid of p14ARF expression (P<0.01). Western blotting showed p14ARF upregulates p53 expression. Conclusion Combined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.

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作者 张群华 [1] 倪泉兴 [1] 甘军 [1] 沈兆忠 [1] 罗建民 [1] 金忱 [1] 张妞 [1] 张延龄 [1] 学术成果认领
作者单位 Center for Pancreatic Cancer, Huashan Hospital, Fudan University, Shanghai 200040, China [1]
分类号 R73
栏目名称 ORIGINAL ARTICLES
发布时间 2003-10-31
基金项目
上海市自然科学基金
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中华医学杂志(英文版)

中华医学杂志(英文版)

2003年116卷8期

1150-1155页

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