TIP30基因启动子甲基化与大肠癌细胞5-氟尿嘧啶化疗敏感性的关系

Correlation of the methylation status of CpG islands in the promoter region of TIP30 tumor suppressor gene with the 5-Fu chemosensitivity in colorectal cancer cells

目的探讨TIP30启动子CpG岛甲基化状态与大肠癌细胞对5-氟尿嘧啶(5-Fu)敏感性的关系。方法采用MTT法检测HCT116和HT29大肠癌细胞株对5-Fu的敏感性。应用甲基化特异性PCR(MSP)方法,检测2细胞株对5-Fu敏感性有差异的大肠癌细胞株中TIP30基因启动子CpG岛甲基化状态,并用RT-PCR检测其mRNA的表达水平。结果 TIP30基因在HCT116及HT29癌细胞中甲基化状态有差异,其表达水平与启动子CpG岛甲基化状态有关,并且二者对5-氟尿嘧啶敏感度不同。结论 TIP30基因启动子甲基化状态可能影响大肠癌细胞对化疗药物的敏感性,为大肠癌患者的个体化治疗提供了可能。

Objective To explore the relationship between the methylation status of CpG islands in the promoter region of TIP30 genes in colorectal cancer cells and the sensitivity of 5-fluouracil（5-Fu） in the colorectal cancer cells.Methods Two cell lines were used in this study.The methylation profile of TIP30 gene in the 2 colorectal cancer cell lines was determined by methylation specific PCR.The level of TIP30 mRNA was quantified by reverse transcription PCR analysis.Results TIP30 gene displayed differential DNA methylation pattern between the HCT116 and HT29 cell lines.The expression of TIP30 mRNA was correlated with the methylation status of CpG islands.The sensitivity of 5-Fu was different in HCT116 and HT29 cells.Conclusion The results of the present study has demonstrated that DNA methylation pattern of TIP30 gene may affect the sensitivity of 5-Fu in the colorectal cancer cells and may make the individual treatment be possible in patients with colorectal cancer.