Enhancement Of Anticancer Effect Of 5'-deoxy-5-fluorouridine By TNF-α And IFN-γ On Colorectal Carcinoma Cells

Background5'-deoxy-5-fluorouridine (5'-DFUR) is an oral anti-cancer drug, widely used in clinical treatment of gastrointestinal cancer. It is a prodrug of 5-fluorouracil (5-FU), must be activated by thymidine phosphorylase (TP) in cancer tissues and converted into 5-FU. It had been reported that breast cancer and gastric cancer cells express TP , but in colon cancer it is still controversial. We have found in previous studies that in colorectal cancer tissues, TP mainly expressed in stromal cells around cancer nests, especially in macrophages. Although there were many reports having confirmed 5'-DFUR obvious effect of the treatment of colorectal cancer, cancer cells do not express TP the transformation of 5'-DFUR in the organization of colon cancer is not clear. However macrophages can excrete many cytokines ,such as tumor necrosis factor-αInterleukin-1αand Interferon-γ,and these cytokines can enhance the anti-tumour effect of 5'-DFUR by up-regulating thymidine phosphorylase. So we consider the applying of cytokine when doing chemotherapy with 5'-DFUR and will detect whether cytokine can enhance the effect of 5'-DFUR on colorectal carcinoma cells in vitro.Objective :To investigate whether TNF-αand IFN-γcan enhance the effect of 5'-deoxy-5-fluorouridine 5'-deoxy-5-fluorouridine on colorectal carcinoma cells Lovo,SW116,HT29,HCT116 in vitro. MethodsThe drug sensitivity of four colorectal carcinoma cell to 5'-DFUR or 5-FU and combined with TNF-αand IFN-γwas estimated Firstly,2×103 cells with TNF-α, IFN-γwere seeded to each well of 96-well plate and incubated at 37℃for 24hours,then 5'-DFUR or5-FU was added at a 2-fold-serial dilution.After incubation for 96 hours,MTT assay was performed ,and the 50%Inhibition Concentration (IC5o) for each drug was calculated with the linear regression of logarithmic transformation.Results :1. The IC50 of 5-FU on 4orectal carcinoma cell ranged from 1.64~3.50μmol/L while that of 5'-DFUR were 64.98~99.40μmol/L 20.68 to 45.54 times higher than those of 5-FU(P<0.0001)2. The IC50 of 5-FU and that of combined with TNF-α,IFN-γon 4 colorectal carcinoma cell had no difference.(P>0.05)3. The IC50 of 5'-DFUR combined with TNF-α,IFN-γon 4 colorectal carcinoma cell was significantly lower than that of 5'-DFURThe IC50 were down to 32.240%~ 62.351% (P<0.0001)4. The IC50 of 5'-DFUR combined with TNF-αand that of IFN-γon 4 colorectal carcinoma cell had difference. (P<0.05)Conclusions :5'-deoxy-5-fluorouridine can enhance of anticancer effect on colorectal carcinoma cells by TNF-αand IFN-γin vitro.