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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 investigate the changes of chemosensitivity to fluorouracil chemotherapeutic drugs (SMMC-7721) and its relationship with the expression of thymidine phosphorylase (TP) under the action of interferon-α (IFN-α) in hepatocellular carcinoma cells. Methods The expression of TP mRNA in SMMC-7721 cells was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and the chemosensitivity of hepatocellular carcinoma cells to fluorouracil chemotherapeutics was detected by MTT assay. Results IFN-α up-regulated TP mRNA expression in a time-and dose-dependent manner. TP mRNA expression began to increase after SMMC-7721 cells were treated with 10 000 U / ml of IFN-α for 8 h, reaching a peak at 12 h and then maintained at a high level for 72 h. The mRNA expression of TP was significantly increased in hepatoma cells treated with 5000 U / ml and 10 000 U / ml IFN-α for 24 h, which was significantly different from that of IFN-α-treated group (P <0.05). The sensitivity of 5-deoxy-5-fluorouridine (5’-dFUrd) to SMMC-7721 cells was significantly enhanced by IFN-α. Under the action of 10 000 U / ml IFN-α, 50) decreased from (102.1 ± 18.4) μmol / L to (34.2 ± 4.1) μmol / L, P <0.05). The effect of IFN-α on the sensitivity of 5-fluorouracil (5-FU) was not significant. Compared with the control group (6.3 ± 1.4) μmol / L, 5.8 ± 2.0) μmol / L. Increased sensitivity of cells to 5’-dFUrd was positively correlated with up-regulation of TP mRNA by IFN-α with a correlation coefficient of 0.6 (Pearson test, P = 0.008). Conclusions IFN-α significantly enhances the sensitivity of hepatoma cells SMMC-7721 to 5-FU precursor drug 5’-dFUrd, which is positively correlated with its upregulation of TP mRNA expression in hepatoma cells. IFN-α up-regulated the expression of TP mRNA in SMMC-7721 cells with Time-dose-dependent.