胰腺癌细胞TYMS基因表达与化疗敏感性的关系

THE RELATIONSHIP BETWEEN THYMIDYLATE SYNTHASE MRNA EXPRESSION AND CHEMOSENSITIVITY OF PANCREATIC CARCINOMA CELLS

目的:探讨胸苷酸合成酶(thymidylate synthase,TYMS)在胰腺癌细胞中mRNA表达差异及其表达水平与胰腺癌细胞化疗敏感性的关系。方法:使用Real-time PCR及Taqman探针法检测其TYMS mRNA表达水平,利用CCK-8试剂盒检测6株胰腺癌细胞(AsPC-1,MIAPaCa-2,Capan-1,SU 86.86,PANC-1与COLO 357)对5-FU的化疗敏感性。结果:在6株人胰腺癌细胞中TYMS基因mRNA表达水平各不相同,TYMS基因mRNA表达水平相比较发现,细胞株AsPC-1,MIAPaCa-2,Capan-1,SU 86.86中TYMS mRNA水平低(低TS表达组),而PANC-1与COLO 357中TYMS mRNA表达水平较高(高TS表达组),低TS表达组的细胞在低中高3个不同药物浓度下对5-FU抑制率分别为0.692±0.137,0.781±0.102与0.885±0.083。同浓度下高TS表达组的细胞对5-FU抑制率分别为0.370±0.157,0.548±0.018与0638±0.020。TYMS mRNA表达低的细胞对5-FU化疗敏感性明显高于TS表达高的细胞,差异有统计学意义(P<0.05)。结论:在胰腺癌细胞株中,TYMS mRNA表达水平与其对5-FU的化疗敏感性密切相关。

Objective：To investigate the relationship between the TS mRNA expression levels and chemosensitivity of different pancreatic cancer cells to 5-FU. Methods：The chemosensitivity of six pancreatic carcinoma cell lines to 5-FU in vitro was evaluated with CCK-8 kit. TS mRNA expression of pancreatic carcinoma cells was analyzed by Real-time PCR. Results：Pancreatic carcinoma cells AsPC-1 , MIAPaCa-2 , Capan-1 and SU 86 . 86 expressed low amounts of TS mRNA （ Low TYMS group） . Cells of PANC-1 and COLO 357 expressed high amounts of TS mRNA（ High TYMS group） in six cell lines. The inhibition rates（ IRs） of Low TYMS group cells for low,middle and high dose to 5-FU were 0. 692＆#177;0. 137,0. 781＆#177;0. 102 and 0. 885＆#177;0. 083 respectively. The IRs of High TS Protein group for low,middle and high dose to 5-FU were 0. 370＆#177;0. 157,0. 548＆#177;0. 018 and 0638＆#177;0. 020,re-spectively. IRs of 5-FU tended to be lower in the cells with high TYMS mRNA expression than thosewith low TS mRNA expression. The difference reached statistical significance（P〈0. 05）. Conclusions：TYMS mRNA expression levels were significantly correlated to 5-FU sensitivity in six pancreatic carcinoma cell lines.