Inhibition of inducible NF-κB activity reduces chemoresistance to 5-fluorouracil in human stomach cancer cell line

Hirokazu Uetsuka, Minoru Haisa, Masashi Kimura, Mehmet Gunduz, Yasufumi Kaneda, Takaomi Ohkawa, Munenori Takaoka, Toshihiro Murata, Tetsuji Nobuhisa, Tomoki Yamatsuji, Junji Matsuoka, Noriaki Tanaka, Yoshio Naomoto

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

5-fluorouracil (5-FU) is used for the treatment of stomach and colon cancer, but many tumors are resistant to this chemotherapeutic agent. 5-FU induces apoptosis of several cancer cell lines, while some chemotherapeutic agents are known to activate the transcriptional factor NF-κB, which strongly suppresses apoptosis in vitro. In the present study, we investigated the relationship between activation of NF-κB and chemoresistance to 5-FU in human stomach cancer cell lines, NUGC3 (5-FU sensitive) and NUGC3/5FU/L (5-FU resistant). Treatment with 5-FU for 9-12 h caused activation of inducible NF-κB in NUGC3/5FU/L cells but not in NUGC3 cells. 5-FU also resulted in an increase in the number of TUNEL-positive cells and enhanced caspase-3 activity 3- to 5-fold in NUGC3 cells but not NUGC3/5FU/L cells. Moreover we also demonstrated that the inhibition of inducible NF-κB activation by using a NF-κB decoy could induce apoptosis and reduce chemoresistance against 5-FU. Our results suggest that 5-FU chemoresistance can be overcome by inhibition of inducible NF-κB activation, and that the use of the NF-κB decoy combined with 5-FU treatment is a new molecular and gene therapeutic strategy aimed at treatment of human stomach cancers resistant to 5-FU.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalExperimental Cell Research
Volume289
Issue number1
DOIs
Publication statusPublished - Sep 10 2003

Keywords

  • 5-fluorouracil (5FU)
  • Apoptosis
  • Chemoresistance
  • NF-κB
  • NF-κB decoy

ASJC Scopus subject areas

  • Cell Biology

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