摘要
目的甲状腺激素(thyroid hormones,THs)对肿瘤发生发展的作用机制尚存争议。本研究探讨THs对Ras癌基因诱导小鼠肝肿瘤发生发展的影响作用。方法采集3、5、7、9个月龄的非转基因和H-ras12V转基因雄鼠(48只)的肝组织和血清样本,统计肝/体质量比,并用酶联免疫法检测血清中总T3、T4水平和游离T3、T4水平;RT-qPCR法和蛋白质印迹法检测9个月龄的非转基因和转基因雄鼠肝组织中THs结合蛋白(thyroid binding globulin,TBG)的mRNA水平和Cyclin D1的蛋白水平。将36只SPF级3个月龄转基因雄鼠按随机数表法分为对照组、甲亢组(饲喂甲状腺片)、甲减组(饲喂丙硫氧嘧啶片),每组12只,处理4个月,7个月龄时采样,检测小鼠血清中总T3和T4水平,统计肝/体质量比、肝肿瘤大小及数量。结果 3、5、7、9个月龄的转基因雄鼠肝/体质量比随月龄的增大逐渐增高,并显著高于同月龄非转基因雄鼠,P<0.01。与9个月龄的非转基因雄鼠相比,同月龄转基因雄鼠血清中总T3和T4水平显著升高(P<0.01),但游离T3和T4水平没有显著变化。与9个月龄的非转基因雄鼠肝组织及转基因雄鼠的肝癌旁组织相比,肝癌组织中TBG的mRNA表达水平和Cyclin D1蛋白水平都显著升高,P<0.01。与对照组相比,甲亢组的T3和T4水平显著升高(P<0.05),甲减组的显著降低,P<0.05。与甲减组相比,甲亢组的肝/体质量比和肝肿瘤总数都显著下降,P<0.05。与甲减组相比,甲亢组直径≥2mm的肝肿瘤数量显著下降(P<0.05),但<2mm的肝肿瘤数量差异无统计学意义。结论 THs对Ras癌基因诱导的肝肿瘤发展具有显著抑制作用,但对肝肿瘤发生没有显著影响。
OBJECTIVE To investigate the effects of thyroid hormones on ras oncogene induced hepatic tumorigenesis and development. METHORDS The liver tissues and serum samples of 3, 5, 7, 9-month-age non-transgenie and H-ras12V transgenic male mice （48） were collected. The liver/body weight ratio and levels of total and free serum T3, T4 were detected. The mRNA levels of TBG and the protein levels of Cyclin D1 in the liver tissues of 9 month age now transgenic and H rasl2V transgenic male mice were detected by RT-qPCR and Western blot. Thirty-six SPF-grade 3-month-age transgenic male mice were randomly divided into control group, hyperthyroidism group （feeding thyroid tab lets） and hypothyroidism group （feeding propyhhiouracil tablets）, 12 in each group, and treated for 4 months and sam pled at 7-month-age. The levels of total serum T3, T4, liver / body weight ratio,and number and size of liver tumors were detected. RESULTS The liver/body weight ratio of 3, 5, 7, 9-month-age transgenic male mice were gradually in- creased along with aging and significantly higher than that of age matched non-transgenic male mice （P〈0.01）. Com pared to the non-transgenic male mice, levels of total serum T3, T4 of 9-month-age transgenic male mice increased significantly （P〈0.01） ,but free serum T3, T4 levels had no significant changes. Compared to the liver tissues of 9 month age non-transgenic male mice and the peri-tumor tissues of transgenic male mice, the mRNA levels of TBG and the protein levels of Cyclin D1 were significantly increased in liver tumor tissues （P〈0.01）. Compared to the control group, serum T3 and T4 levels in hyperthyroid group were increased significantly （P〈0.05） and in hypothyroidism group decreased significantly （P〈0.05）. Compared to the control group, the liver/body weight ratio and total number of liver tumors of hyperthyroid group were decreased significantly （P〈0.05）. Compared to control group and hypothyroidism group, the number of liver tumors more than 2 mm in size in hyperthyroid group was significantly decreased （P〈0.05）, but there was no significant difference in the number of liver tumors less than 2 mm of size. CONCLUSION Thyroid hormones have significant suppression effects on ras oncogene induced hepatic tumor development, hut not tumorigenesis.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2015年第20期1596-1601,共6页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30872950)
