DAC及TSA对结肠癌细胞系中TIP30基因表达的影响及伊立替康敏感性探讨  

The effects of DAC and TSA on expression of TIP30 gene and CPT-11 sensibility in human colon cancer cell lines

作　　者：马一杰[1] 吕慧芳[1] 尚艺曼[1] 罗素霞[1] 陈小兵[1] 颜才华[1] 

机构地区：[1]郑州大学附属肿瘤医院(河南省肿瘤医院)肿瘤内科,河南郑州450008

出　　处：《胃肠病学和肝病学杂志》2013年第3期240-242,共3页Chinese Journal of Gastroenterology and Hepatology

基　　金：河南省医药卫生河南省医药卫生重大攻关项目;卫生部科研基金资助项目(WKJ2011010012)

摘　　要：目的探讨DAC及TSA对结肠癌细胞系中抑癌基因TIP30表达的影响,以及与伊立替康敏感性的关系。方法 DAC及TSA处理体外培养的结肠癌细胞系HCT116及HT29,RT-PCR法检测结肠癌细胞系HCT116及HT29药物干预前后抑癌基因TIP30表达情况的变化。MTT法检测结肠癌细胞株HCT116和HT29在不同浓度CPT-11下的凋亡情况,绘制生长抑制曲线并计算半数抑制浓度。结果 HCT116及HT29细胞系经DAC及DAC和TSA联合作用后使原来不表达或低表达的抑癌基因TIP30重新表达或表达增强;结肠癌细胞系HT29与HCT116相比伊立替康敏感性较强,DAC处理后2个细胞系伊立替康敏感性均增强。结论TIP30基因的异常甲基化是结肠癌发生发展中的常见现象,结肠癌细胞系中TIP30启动子甲基化可能是基因失活的主要调控机制,DAC单独干预和DAC及TSA联合干预效果相似,均能显著增加高甲基化抑癌基因的重新表达。基因甲基化水平可能与化疗敏感性相关。Objective To explore the effect of DAC and TSA on expression of TIP30 gene in colon cancer cell. Methods Human colon cancer cell lines HCTll6 and HT29 were treated with different concentrations of DAC and TSA, the expression of TIP30 gene was detected by RT-PCR. MTT assay was used to detect the sensitivity of colon cells to CPT-11 in HCTll6 and HT29. Results TIP30 mRNA was expressed in colon cancer cell lines HCTll6 and HT29 after DAC and TSA treatment, but it was undetectable or low expression before treatment. The sensitivity to CPT-11 was proved to be different in HCTII6 and HT29 cells, and tended to be improved by DAC treatment. Conclusion Aberrant methylation of TIP30 gene is a common event in the occurrence and progression of colon cancer. The methylation of pro- moter region in CpG island is a main cause of TIP30 gene transcriptional inactivation. The effects of DAC and the combi- nation of DAC and TSA are similar to dramatically enhance expression of mRNA in human colon cancer cell. The chem- osensitivity in colon cells may correlate with its methylation status of gene.

关 键 词：结肠癌 甲基化 伊立替康 TIP30基因 

分 类 号：R735.35[医药卫生—肿瘤]