索拉非尼诱导甲状腺癌细胞铁死亡的作用  

Effect of sorafenib on ferroptosis of thyroid cancer cells

作　　者：严丽[1] 冀宏[1] 郝芳[1] 赵苏远[1] 晋潇 张文涛 Yan Li;Ji Hong;Hao Fang;Zhao Suyuan;Jin Xiao;Zhang Wentao(Department of Thyroid and Breast Surgery,the Second Hospital of Hebei Medical University,Shijiazhuang 050004,China)

机构地区：[1]河北医科大学第二医院甲状腺乳腺外科,石家庄050004

出　　处：《中华实验外科杂志》2021年第11期2153-2155,共3页Chinese Journal of Experimental Surgery

基　　金：河北省自然科学基金(H2018206184)。

摘　　要：目的探讨索拉非尼诱导甲状腺癌TPC-1细胞铁死亡的作用。方法体外培养人甲状腺癌TPC-1细胞,对其处理并分为索拉非尼组和阴性对照组,利用细胞计数试剂盒(CCK-8)实验检测细胞活性;以二氯荧光素(DCFH-DA)探针检测活性氧(ROS)的产生;应用蛋白质印迹法(Western blot)实验检测铁死亡相关蛋白ACSL4、SLC7A11及GPX4的表达水平;以丙二醛(MDA)试剂盒检测细胞内MDA含量。统计数据中多组间均数比较采用方差分析,两组间比较采用t检验。结果索拉非尼干预处理组细胞吸光度值(1.29±0.17)明显低于对照组细胞吸光度值(1.86±0.23,t=2.695,P<0.05);TPC-1细胞经过索拉非尼干预处理后,ROS的荧光强度(1.833±0.293)明显高于对照组(0.825±0.186,t=2.801,P<0.05);蛋白印迹法检测结果表明,索拉非尼干预处理后ACSL4蛋白表达水平(0.954±0.091)高于对照组细胞(0.442±0.132,t=5.314,P<0.05),SLC7A11的蛋白表达水平(0.293±0.087)明显低于对照组细胞(0.897±0.098,t=7.916,P<0.05),GPX4的蛋白表达水平(0.325±0.051)同样低于对照组细胞(0.893±0.069,t=9.325,P<0.05)。MDA检测结果表明,索拉非尼干预处理组MDA水平(30.661±3.192)明显高于对照组(19.285±1.406,t=5.901,P<0.05)。结论索拉非尼可促进甲状腺癌细胞铁死亡进程,加快甲状腺癌细胞死亡。Objective To observe the effect of sorafenib on ferroptosis in thyroid cancer TPC-1 cells,and to provide a new strategy for the treatment of thyroid cancer.Methods Thyroid cancer TPC-1 cells were cultured in vitro,treated and divided into sorafenib group and negative control group,and cell counting kit-8(CCK-8)assay was used to detect cell viability;Dichlorofluorescein(DCFH-DA)probe was used to detect reactive oxygen species(ROS)production;Western blotting experiment was used to detect the protein expression levels of ACSL4,SLC7A11 and GPX4;Malondialdehyde(MDA)kit was used to detect the content of MDA in thyroid cancer cells.Analysis of variance was used for the mean comparison between multiple groups,and t-test was used for the comparison between the two groups.Results The cell absorbance value of sorafenib intervention group(1.29±0.17)was significantly lower than that of control group(1.86±0.23,t=2.695,P<0.05);The fluorescence intensity of ROS in TPC-1 cells treated with sorafenib(1.833±0.293)was significantly higher than that in the control group(0.825±0.186,t=2.801,P<0.05);Western blotting experiments showed that the expression level of ACSl4 protein(0.954±0.091)after sorafenib intervention was higher than that in the control group(0.442±0.132,t=5.314,P<0.05),and the protein expression level of SLC7A11(0.293±0.087)was significantly lower than that in the control group(0.897±0.098,t=7.916,P<0.05),the protein expression level of GPx4(0.325±0.051)was also lower than that of control cells(0.893±0.069,t=9.325,P<0.05).The results of MDA detection showed that the expression level of MDA in sorafenib intervention group(30.661±3.192)was significantly higher than that in control group(19.285±1.406,t=5.901,P<0.05).Conclusion Sorafenib can promote the ferroptosis process of thyroid cancer cells and accelerate the death of thyroid cancer cells.

关 键 词：甲状腺癌 索拉非尼 铁死亡 活性氧簇 

分 类 号：R736.1[医药卫生—肿瘤]