5-氮杂-2’-脱氧胞苷对人甲状腺癌TPC-1细胞生长及KLF4基因表达的调节作用  

Effects of 5-Aza-CdR on growth of TPC-1 cell line and KLF4 expression

作　　者：李明闯[1] 王瑞娟[1] 陈国[1] 张青松[1] 吴迪[1] 吕晶[1] 霍彦平[1] 殷德涛[2] 

机构地区：[1]郑州大学附属郑州中心医院乳腺甲状腺外科,450052 [2]郑州大学第一附属医院甲状腺外科、河南省高等学校临床医学重点学科开放实验室,450052

出　　处：《中华内分泌外科杂志》2015年第6期480-483,492,共5页Chinese Journal of Endocrine Surgery

基　　金：国家自然科学基金（81372863）;郑州市科技领军人才项目（131PLJRC676）

摘　　要：目的抑癌基因甲基化具有可逆性，相关药物可逆转甲基化使失活的基因重新表达。本研究观察去甲基化制剂5-氮杂-2’-脱氧胞苷（5-Aza-CdR）对体外培养的人甲状腺癌TPC-1细胞增殖的影响，及5-iza-CdR对KLF4基因mRNA和蛋白表达水平的影响。方法使用不同浓度的5-Aza-CdR处理TPC-1细胞，采用MTF检测5-Aza-CdR对细胞增殖的影响，利用RT-PCR及蛋白质印迹法（Westemblot）方法检测KLF4基因mRNA和蛋白表达的水平。结果5-Aga—CdR作用于TPC-1细胞24、48及72h后，TPC-1细胞增殖受抑制，且在一定范围内抑制率呈浓度和时间依赖性；TPC-1细胞经5-Aza．CdR干预后，KLF4基因mRNA和蛋白表达水平升高，差异有统计学意义（P〈0．05）。结论5-Aza-CdR能抑制TPC-1细胞增殖，其作用可能是通过去甲基化上调抑癌基因KLF4的表达实现，为甲状腺癌的治疗提供了新思路。Objective Methylation of anti-oncogene can be demethylated by related drugs which can help the inactivated gene to express again. This study aims to study the effects of the demethylating agent 5-Aza- 2＇-deoxycytidine on the growth of human thyroid papillary cancer cell line TPC-1 and mRNA and protein expres- sion of KLF4. Methods TPC-1 ceils were treated with different concentration of 5-Aza-CdR. MTI＂ was used to detect the influence of 5-Aza-CdR on cell proliferation. RT-PCR was used to detect mRNA and protein expression levels of KLF4. Results After being treated with 5-Aza-CdR for 24 hours, 48 hours, and 72 hours, the growth of TPC-1 cells was inhibited and the inhibition was in time and concentration depended manner. After treatment with 5-Aza-CdR, mRNA and protein expression levels of KLF4 were increased, and the difference had statistical signifieanee（P 〈0. 05 ）. Conclusion 5-Aza-CdR can inhibit the cell viability of TPC-1 cells through upregulat- ing KLF4 expression, which may provide experimental basis for 5-Aza-CdR in treating thyroid cancer.

关 键 词：KLF4基因 去甲基化 5-氮杂-2’-脱氧胞苷 甲状腺癌 

分 类 号：R736.1[医药卫生—肿瘤]