干扰素α2a对人结肠癌细胞胸苷磷酸化酶表达和5＇脱氧氟尿苷抗癌活性的影响

Influence of interferon-α2a on thymidine phosphorylase expression and anticancer activity of 5＇-deoxy-fluorouridine in human colon carcinoma cell lines LOVO and SW480

目的探讨干扰素-α2a（IFN-αt2a）对人结肠癌细胞胸苷磷酸化酶（TP）mRNA表达水平以及5＇-脱氧氟尿苷（5’-DFUR）和氟尿嘧啶（5-FU）抗癌效应的影响。方法不同剂量IFN-α2a分别处理人结肠癌细胞LOVO和SW480．荧光定量PCR检测TPmRNA表达水平：MTT法检测联合应用IFN-α2a前后5．FU和5＇-DFUR对LOVO和SW480抑制作用的半数有效浓度（IC50）变化情况。结果与0U／mlIFN-α2a浓度组相比．500U／ml及5000U／ml组可明显上调LOVO和SW480细胞TPmRNA表达（P〈0．01），而50U／ml则对上述两种细胞TPmRNA表达水平无明显影响（P〉0．05）。联合应用浓度为20U／ml的IFN-α2a后．5．FU对LOVO和SW480细胞的IC50无明显改变（P〉0．05）．但5’-DFUR的IC50则明显降低（P〈0．05）。结论IFN-α2a能上调结肠癌细胞TPmRNA的表汰水平并可使5＇-DFIIR对结肠痛细胞的1C50明显下降而对5-FI7则无明显影响。

Objective To detect the effect of interferon-α2a （IFN-α2a） on thymidine phosphorylase （TP） mRNA expression levels and the anticancer activity of 5-fluorouracil （5-FU） and 5＇- deoxy-fluorouridine（5＇-DFUR） in human colon carcinoma cell lines LOVO and SW480. Methods Two human colon cancer cell lines LOVO and SW480 were cultured and treated with IFN-α2a at a series of dosage, and fluorescence quantitative PCR was carried out to detect the TP mRNA expression levels in these 2 cell lines. Then MTY assay and software Templet were used to determine the change of 50% inhibition concentration of 5-FU or 5＇-DFUR combined with IFN-α2a on the two cell lines. Results The TP mRNA expressions were up-regulated significantly by IFN-α2a at the doses of 500 U/ml and 5000 U/ml in LOVO（P〈0.01）. Compared with untreated cells（IFN-α2a 0 U/ml）, no significance was found for TP mRNA expression levels in LOVO and SW480 treated by IFN-α2a at the dose of 50 U/ml （P〉0.05）. There was no significant difference for TP mRNA expression in SW480 between the dose of 0 U/ml and 500 U/ml of IFN-α2a （P〉0.05）, while a significant increace was detected at the dose of 5000 U/ml （P〈0.O1）. No significant difference was found for the IC50 values after treatment of 5-FU combined with IFN-α2a （20 U/ml） on LOVO and SW480 compared with 5-FU alone, while the ICSO values after treatment of 5＇-DFUR combined with IFN-α2a decreased significantly compared with 5＇- DFUR alone （P〈0.05）. Conclusion There is no direct inhibition effect of IFN-α2a on LOVO and SW480 in vitro, while it can up-regulate TP mRNA expression levels both in LOVO and SW480, and enhance the antieancer effect of 5＇-DFUR on these 2 cell lines.