Overexpression of Interferon Regulatory Factor 1 Enhances Chemosensitivity to 5-fluorouracil in Gastric Cancer Cells

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.