131I联合甲磺酸阿帕替尼对难治性甲状腺癌细胞的抑制作用及机制研究

Inhibitory effect and mechanism of 131I combined with apatinib on refractory thyroid cancer cells

目的探讨131I联合血管生成抑制剂甲磺酸阿帕替尼对难治性甲状腺癌细胞的抑制作用及其机制。方法将难治性甲状腺癌细胞分为对照组、131I组、阿帕替尼组及131I联合阿帕替尼治疗组(联合组),使用噻唑蓝(MTT)法检测各组肿瘤细胞治疗24 h、48 h后的增殖率;采用免疫荧光方法及蛋白印迹法检测各组细胞凋亡蛋白Caspase-3和血管生成蛋白VEGF的表达。结果联合组处理后细胞的增殖率明显低于其它各组,差异具有统计学意义(P<0.05)。联合组Caspase-3蛋白的表达含量明显高于其它各组(P<0.01),联合组VEGF蛋白的相对表达量显著低于其它各组(P<0.01)。结论131I联合甲磺酸阿帕替尼作用于难治性甲状腺癌细胞时具有协同增效作用,131I联合甲磺酸阿帕替尼通过上调促凋亡蛋白Caspase-3,下调VEGF的表达水平以达到增强131I抑制难治性甲状腺癌的增殖作用,从而为难治性甲状腺癌的临床治疗提供较好的策略。

Objective The objective of this study was to investigate the inhibitory effect of 131I combined with angiogenesis inhibitor apatinib on refractory thyroid cancer cells and its mechanism.Methods The refractory thyroid cancer cells were divided into the control group,131I group,apatinib group,and 131I combined with apatinib group(combined group).After treatment for 24 and 48 h,the proliferation of thyroid cancer cells was determined by thiazolyl blue(MTT)assay.The expression of Caspase-3 and VEGF proteins was determined by immunofluorescence and Western blot.Results The proliferative rate of refractory thyroid cancer cells in the combined group was significantly lower than that in the other groups,and the difference was statistically significant(P<0.01).The expression of Caspase-3 protein in the combined group was significantly higher than that in the other groups(P<0.01),and the expression of VEGF protein in the combined group was significantly lower than that in the other groups(P<0.01).Conclusion 131I combined with apatinib has synergistic effect on refractory thyroid cancer cells.This combination can up-regulate the pro-apoptotic protein Caspase-3 and down-regulate the expression of VEGF protein to inhibit the proliferation of refractory thyroid cancer cells.Thus,this will provide a better strategy for clinical treatment of refractory thyroid cancer.