三苯氧胺抑制雌激素受体阴性的甲状腺癌生长  

Tamoxifen inhibits the growth of ER negative thyroid carcinomas in vitro and in vivo

作　　者：沈美萍[1] 武正炎[1] 侯大卫[1] 刘翠萍[2] 

机构地区：[1]南京医科大学第一附属医院普外科,江苏南京210029 [2]南京医科大学第一附属医院内分泌科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2007年第5期467-471,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省教育厅高校自然科学研究计划项目资助(02KB320004)

摘　　要：目的:研究三苯氧胺(tamoxifene,TAM)对雌激素受体阴性的甲状腺乳头状癌和滤泡状癌的体内外作用,并初步探索其作用机制。方法:①体外实验:4-甲基偶氮四唑蓝(MTT)细胞增殖试验观察TAM对甲状腺乳头状癌细胞(IHH-4)和甲状腺滤泡状癌细胞(FTC3-133)生长的影响,流式细胞仪DNA定量法观察TAM作用后甲状腺癌细胞周期的变化和晚期凋亡的发生。免疫组织化学法和RT-PCR的方法检测2株细胞中雌激素受体(ER)的表达。②体内实验:5周龄BALB/c雌性裸鼠皮下接种甲状腺乳头状癌细胞IHH-4,肿瘤生长后,处理组予TAM5mg/(kg·d)灌胃,对照组予等体积安慰剂,连续5周观察肿瘤体积的生长和小鼠体重的变化,并最终比较两组间肿瘤的重量。结果:①体外实验:免疫组化法和RT-PCR法检测IHH-4和FTC-133细胞中雌激素受体均为阴性;TAM明显抑制两株甲状腺癌细胞增殖,呈时间和剂量依赖性;TAM使两株甲状腺癌细胞阻滞于G1期,并且诱导FTC3-133细胞的凋亡。②体内实验:TAM抑制甲状腺癌细胞种植瘤的生长。结论:TAM抑制甲状腺癌生长,并通过非依赖雌激素受体途径发挥作用。Objectives：To investigate the effects of tamoxifen （TAM） on the growth of estrogen receptor （ER） negative thyroid carcinomas and the mechanisms involved. Methods：In vitro experiments, papillary thyroid carcinoma cells （IHH-4） and follicular thyroid carcinoma cells （FFC-133） were treated with tamoxifen in different doses and different lengths of time, using the dimethylthiazol-diphehetrazolium bromide （MTF） method to observe the cell proliferation. Cell cycle and apoptosis were analysed with flow cytometric DNA studies. In vivo experiments the papillary thyroid carcinoma cells were injected into the nude mice subcutaneously, and the mice had been feed with TAM [5 mg/（kg·d）] daily since the second week. The tumor volumes were calculated weekly. Finally the mice were sacrificed and the tumors were weighed separately. Results：In vitro,TAM inhibited the proliferation of the IHH-4 and FFC-133 cell lines in dose-dependent and time-dependent pattern. TAM inhibited the growth of the IHH-4 and FFC-133 cell lines by blocking the cell cycle in G1 phase. Immunohistochemistry and RT-PCR studies showed the ER negative in both cell lines. In vitro,TAM also inhibited the growth of IHH-4 xenografts in nude mice. Conclusions：TAM inhibits the growth of thyroid carcinoma in vitro and in vivo. TAM acts independent of estrogen receptor and could be a potential choice for the treatment of the aggressive thyroid carcinomas clinically.

关 键 词：TAM 甲状腺癌 细胞周期 体内试验 体外实验 

分 类 号：R736.1[医药卫生—肿瘤] Q74[医药卫生—临床医学]