【摘要】 目的 探讨17β-雌二醇对甲状腺癌细胞增殖的影响，及其与三叶因子3（TFF3）基因启动子甲基化水平的关系。方法 将甲状腺癌TPC-1、BCPAP、FTC-133细胞分为4组：空白组（未加任何处理）、对照组（含浓度<0.05%二甲基亚砜的培养基）和低、高剂量实验组(1和100 nmol·L^-1 17β-雌二醇)。用甲基化特异性聚合酶链反应分析17β-雌二醇处理前后3株细胞TFF3基因启动子区甲基化水平，用生长曲线检测17β-雌二醇对3株细胞增殖的影响。结果 TFF3基因启动子甲基化水平随17β-雌二醇浓度的升高而降低。在TPC-1细胞中，低、高剂量实验组的TFF3基因启动子区甲基化百分比分别从空白组和对照组的（53.34±0.62）%,（54.62±3.11）%降至（37.12±1.19）%和（27.84±0.73）%,BCPAP细胞的TFF3基因启动子区甲基化百分比从空白组和对照组的（56.04±0.93）%,（58.08±0.89）%降至（50.33±0.55）%和（26.36±0.74）%,FTC-133细胞的TFF3基因启动子区甲基化百分从空白组和对照组的（73.28±0.36）%,（71.64±0.54）%降至（61.33±0.56）%和（51.28±0.62）%。在3种细胞中，低、高剂量实验组的上述指标与对照组相比，差异均有统计学意义（P<0.05,P<0.01）。生长曲线结果显示，17β-雌二醇能促进甲状腺癌细胞增殖。对照组在第5天时TPC-1,BCPAP和FTC-133细胞的汇合度分别为（50.04±2.83）%,（30.02±4.97）%和（25.09±2.94）%,高剂量实验组在第5天时TPC-1,BCPAP和FTC-133细胞的汇合度分别上升到（100.00±2.16）%,（90.08±3.56）%和（40.03±2.93）%,高剂量实验组的上述指标与对照组相比，差异均有统计学意义（均P<0.01）。结论 17β-雌二醇能通过降低TFF3基因启动子区CPG位点的DNA甲基化水平，促进癌细胞增殖。更多还原

【Abstract】 Objective To investigate the effect of 17β-estradiol on proliferation of thyroid cancer （TC） cells,and to explore its relationship with the methylation levels of trefoil family factor 3 （TFF3） promoter in different TC cell lines.Methods The 3 types of TC cells,TPC-1,BCPAP and FTC-133 were divided into 4 groups:blank group （without any treatment）,control group （media containing<0.05%dimethylsulfoxide）,experimental-L group (1 nmol·L^-1) and experimental-H group (100 nmol·L^-1).The methylation levels of TFF3 gene promoter region of TC cells before and after 17β-estradiol treatment were analysed by methylation-specific polymerase chain reaction.Growth curve experiment was used to detect the effect of 17β-estradiol on the proliferation of three types of TC cells.Results The methylation level of the TFF3 gene promoter decreased with the increase of 17β-estradiol concentration.In TPC-1 cells,the methylation percentage of TFF3 gene promoter region in blank and control groups were （53.34±0.62）%and （54.62±3.11）%,which in experimental-Land experimental-H groups decreased to （37.12±1.19）%and （27.84±0.73）%,respectively.In BCPAP cells,the methylation percentage of TFF3 gene promoter region in blank and control groups were （56.04±0.93）%and（58.08±0.89）%,which in experimental-L and experimental-H groups decreased to （50.33±0.55）%and（26.36±0.74）%,respectively.In FTC-133 cells,the methylation percentage of TFF3 gene promoter region in blank and control groups were （73.28±0.36）%and （71.64±0.54）%,which in experimental-L and experimental-H groups decreased to （61.33±0.56）%and （51.28±0.62）%,respectively.Among the three cells,the differences of above indexes were statistically significant between the experimental-L,-H groups and control group （P<0.05,P<0.01）.The results of growth curve indicated that 17β-estradiol could stimulate the proliferation of thyroid cancer cells.The confluences of TPC-1,BCPAP and FTC-133 cells at the 5^thday were（50.04±2.83）%,（30.02±4.97）%,（25.09±2.94）%in blank group,but in group experimental-H,these values rised to （100.00±2.16）%,（90.08±3.56）%,（40.03±2.93）%.Also,there were statistically significant differences between experimental-H group with blank group （all P<0.01）.Conclusion 17β-estradiol may promote TC cell proliferation by reducing the DNA methylation level of CPG sites in the promoter region of TFF3 gene.更多还原