Interferon Gamma Enhances The Cytotoxicity Of 5-fluorouracil Against Human Gastric Cancer Cells By Up-regulation Of Thymidine Phosphorylase

Objective:To investigate the regulative effect of interferon gamma (IFN-γ)on the expression of thymidine phosphorylase(TP)and its relationship with the anti-cancer effect of 5-fluorouracil(5-FU)on MKN45 gastric cancer cells.Methods:TP mRNA and protein expressions were determined by reverse transcription-polymerase chain reaction(RT-PCR)and Western blot,respectively.Cytotoxicity of 5-FU against MKN45 cells was evaluated by MTT assay.FITC AnnexinV/PI were used for measuring apoptosis by flow cytometry.Results:The expressions of TP mRNA and protein were concomitantly elevated in MKN45 cells after IFN-γtreatment(P＜0.05).IFN-γhas increased TP expressionin a dose and time dependent manner.IFN-γdecreased IC50 of 5-FU significantly[from(13.3448±0.4558)mmol/L to (4.0369±0.1674)mmol/L,(P＜0.05)]in MKN45 cells.Treatment of IFN-γ/5-FU combination result in increasion of apoptosis rate in gastric cancer cells.Conclusions:IFN-γenhances cytotoxicity of 5FU against human gastric cancer cells through induction of TP,which suggests IFN-γ/5-FU combination treatment may result in better chemotherapeutic effect in human gastric cancers.