干扰素-α在肝癌细胞对5′-脱氧-5-氟尿苷敏感性及其胸苷磷酸化酶表达的作用  

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

作　　者：肖永胜[1] 周俭[1] 樊嘉[1] 赵燕[1] 孙瑞霞[1] 刘银坤[1] 叶胜龙[1] 汤钊猷[1] 

机构地区：[1]复旦大学附属中山医院外科,肝癌研究所,上海200032

出　　处：《中华医学杂志》2007年第30期2098-2100,共3页National Medical Journal of China

基　　金：高等学校博士点专项科研基金(20030246052);上海市教委基金(02JG05035)

摘　　要：目的探讨肝癌细胞 SMMC-7721在干扰素-α(IFN-α)的作用下,对氟尿嘧啶类化疗药物敏感性的变化,及其与胸苷磷酸化酶(TP)表达水平的关系。方法利用逆转录聚合酶链反应(RT-PCR)检测 SMMC-7721细胞 TP mRNA 表达水平,利用 MTT 法检测肝癌细胞对氟尿嘧啶类化疗药物的敏感性。结果 IFN-α上调 TP mRNA 表达具有时间-剂量依赖性。10 000 U/ml 的 IFN-α处理SMMC-7721细胞8 h 后 TP mRNA 表达水平开始升高,至12 h 达到峰值,此后维持较高水平至72 h。5000 U/ml 与10 000 U/ml IFN-α处理肝癌细胞24 h,TP mRNA 表达水平显著升高,与未用 IFN-α处理组相比,差异有统计学意义(P<0.05)。IFN-α能明显提高 SMMC-7721细胞对5′-脱氧-5-氟尿苷(5′-dFUrd)的敏感性,在10 000 U/ml IFN-α作用下,5′-dFUrd 的 IC_(50)由(102.1±18.4)μmol/L 降低至(34.2±4.1)μmol/L(P<0.05)。而 IFN-α对5-氟尿嘧啶(5-FU)的敏感性影响不大,IC_(50)与对照组(6.3±1.4)μmol/L 相比,10 000 U/ml IFN-α作用时为(5.8±2.0)μmol/L。细胞对5′-dFUrd 敏感性的增加与 IFN-α上调 TP mRNA 正相关,相关系数为0.6(Pearson 检验 P=0.008)。结论 IFN-α显著增强肝癌细胞 SMMC-7721对5-FU 前体药物5′-dFUrd 的敏感性,与其上调肝癌细胞 TP mRNA 表达水平正相关;IFN-α上调 SMMC-7721细胞 TP mRNA 表达水平具有时间-剂量依赖性。Objective 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-α）, and its relationship with the expression of thymidine phosphorylase （TP）. Methods TP mRNA expression was determined by RT-PCR. Cytotoxicity of 5′-dFUrd, and 5-FU against SMMC-7721 cells was evaluated by MTT assay. Results Expression levels of TP mRNA was elevated in SMMC-7721 cells after cultured with IFN-ct, 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-α, 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-α, the level of TP mRNA rose at 8hr, reached the peak value at 12hr, and remained high level up to 72hr. IFN-α enhanced the sensitivity of SMMC-7721 cells to 5＇-dFUrd with dose-dependent increase. IFN-α （ 10 000 U/ml） reduced IC50 of 5′-dFUrd from （ 102. 1 ± 18.4） μmol/L to （34. 2 ± 4. 1 ） μmol/L （ P 〈0. 05 ）. There was no obvious relation between use of IFN-α and 5-FU sensitivity. ICs0 of 5-FU was （5.8± 2.0）μmol/L and （6.3 ± 1.4）μmol/L in with IFN-α （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. Conclusion IFN-α enhanced cytotoxicity of 5′-dFUrd against SMMC-7721 ceils positively related to its induction of TP mRNA.

关 键 词：胸苷磷酸化酶 干扰素-Α 药物疗法 癌 肝细胞 

分 类 号：R735.7[医药卫生—肿瘤]