Interferon alpha enhances the sensitivity of SMMC-7721 hepatocellular carcinoma cells to 5'-deoxy-5-fluorouridine related to up-regulation of thymidine phosphorylase

Abstract

To observe changes of sensitivity to 5'-deoxy-5-fluorouridine (5'-dFUrd), and 5-fluorouracil (5-FU) in SMMC-7721 hepatocellular carcinoma cells by interferon alpha (IFN-alpha), and its relationship with the expression of thymidine phosphorylase (TP). TP mRNA expression was determined by RT-PCR. Cytotoxicity of 5'-dFUrd, and 5-FU against SMMC-7721 cells was evaluated by MTT assay. Expression levels of TP mRNA was elevated in SMMC-7721 cells after cultured with IFN-alpha, which was a concentration- and time-dependent increase. After SMMC-7721 cells was treated in the concentration of 5000 U/ml, and 10 000 U/ml IFN-alpha, the level of TP mRNA was significantly higher than that in untreated control (P < 0.05). When SMMC-7721 cells was cultured with the concentration 10 000 U/ml IFN-alpha, the level of TP mRNA rose at 8hr, reached the peak value at 12hr, and remained high level up to 72hr. IFN-alpha enhanced the sensitivity of SMMC-7721 cells to 5'-dFUrd with dose-dependent increase. IFN-alpha (10 000 U/ml) reduced IC(50) of 5'-dFUrd from (102.1 +/- 18.4) micromol/L to (34.2 +/- 4.1) micromol/L (P < 0.05). There was no obvious relation between use of IFN-alpha and 5-FU sensitivity. IC(50) of 5-FU was (5.8 +/- 2.0) micromol/L and (6.3 +/- 1.4) micromol/L in with IFN-alpha (10 000 U/ml) and control group, respectively. Under the use of interferon, sensitivity to 5'-dFUrd increased positively related to up-regulation of TP mRNA expression. IFN-alpha enhanced cytotoxicity of 5'-dFUrd against SMMC-7721 cells positively related to its induction of TP mRNA.