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

张群华 倪泉兴 甘军 沈兆忠 罗建民 金忱 张妞 张延龄

中华医学杂志(英文版)2003,Vol.116Issue(8):1150-1155,6.
中华医学杂志(英文版)2003,Vol.116Issue(8):1150-1155,6.

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

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

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

作者信息

  • 1. Center for Pancreatic Cancer, Huashan Hospital, Fudan University, Shanghai 200040, China
  • 折叠

摘要

Abstract

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.

关键词

pancreatic cancer/p14ARF/5-fluorouracil

Key words

pancreatic cancer/p14ARF/5-fluorouracil

分类

医药卫生

引用本文复制引用

张群华,倪泉兴,甘军,沈兆忠,罗建民,金忱,张妞,张延龄..p14ARF upregulation of p53 and enhanced effects of 5-fluorouracil in pancreatic cancer[J].中华医学杂志(英文版),2003,116(8):1150-1155,6.

基金项目

This investigation was partly supported by a grant from the Shanghai Science Fundation (No. 004119009). (No. 004119009)

中华医学杂志(英文版)

OAMEDLINESCI

0366-6999

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