Overexpression of interferon regulatory factor 1 enhances chemosensitivity to 5-fluorouracil in gastric cancer cells

J Cancer Res Ther. 2012 Jan-Mar;8(1):57-61. doi: 10.4103/0973-1482.95175.

Abstract

Purpose: To investigate the effects of interferon regulatory factor 1 (IRF-1) gene overexpression on chemotherapeutic sensitivity of gastric cancer cells.

Materials and methods: An AGS cell system with tetracycline-inducible IRF-1 expression (AGS/IRF-1) was established. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of the IRF-1 gene. Chemosensitivity to 5-fluorouracil (5-FU) was assessed by cell proliferation assay and cell apoptosis.

Results: IRF-1 mRNA and protein level were significantly increased in AGS/IRF-1 cells induced with tetracycline. Compared with control cells, the growth inhibition rate of cells with IRF-1 overexpression was significantly increased when treated with 5-FU (P<0.01). Treatment with 5 μmol/l 5-FU resulted in 12.6% apoptotic cells, whereas such treatment after overexpression of IRF-1 resulted in 39.4% apoptotic cells. Moreover, more poly(adenosine diphosphate-ribose) polymerase (PARP) cleavage was seen in cells with IRF-1 overexpression.

Conclusions: Overexpression of IRF-1 enhanced the chemosensitivity of gastric cancer cells to 5-FU through induction of apoptosis.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Gene Expression
  • Humans
  • Interferon Regulatory Factor-1 / genetics*
  • Interferon Regulatory Factor-1 / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • Interferon Regulatory Factor-1
  • RNA, Messenger
  • Poly(ADP-ribose) Polymerases
  • Fluorouracil