核因子κB抑制剂对^131Ⅰ导致甲状腺癌细胞凋亡的协同作用  

Synergistic effects of nuclear factor-kappa B inhibitor on^131Ⅰ induced apoptosis in differentiated thy- roid cancer cells

作　　者：孟召伟[1] 谭建[1] 

机构地区：[1]天津医科大学总医院核医学科,300052

出　　处：《中华核医学与分子影像杂志》2012年第5期374-378,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金（30900376）;天津市科委应用基础及前沿技术研究计划（10JCZDJC19000）;天津医科大学科学基金（2008KY20）

摘　　要：目的研究核因子κB（NF-κB）抑制剂Bay11-7082和^131Ⅰ导致DTC细胞凋亡的效果，并探讨二者的协同作用。方法用Westernblot鉴定^131Ⅰ、Bay11-7082以及两者联合处理DTC细胞24h后细胞内NF-κB调控的凋亡抑制因子[x染色体相关凋亡抑制蛋白（XIAP）和生存素蛋白（stir-vivin）]以及凋亡关键因子[天冬氨酸特异性半胱氨酸蛋白酶（caspase3）和多聚腺苷二磷酸核糖聚合酶（PARP）]相对表达水平的变化，以β-actin作内参，进行半定量分析。用膜黏连蛋白-5-异硫氰酸荧光磺／碘化丙啶双标记染色流式细胞技术鉴定不同方式处理后癌细胞的凋亡变化。多组间均数比较采用单因素方差分析，两两比较采用q检验进行统计分析。结果Westernblot证实对照组DTC癌细胞内XIAP和survivin相对表达水平为（16．62±0．73）％和（15．20±0．53）％，^131Ⅰ作用24h后两者增至（95．22±3．27）％和（71．80±2．76）％，而^131Ⅰ联合Bay11-7082作用后两者分别被抑制至（8．29±0．35）％和（6．87±0．28）％。不同处理方式作用后XIAP和survivin表达水平差异均有统计学意义（F=1823．47和1406．12，P均〈0．01），联合处理组与^131Ⅰ组，对照组两两比较q值13．37至45．38（P均〈0．01）。对照组easpase3的2个亚基p19和p17以及PARP失活水解产物p89相对表达水平为（4．93±0．49）％、（4．67±0．34）％和（4．87±0．64）％，^131Ⅰ作用24h后增高至（25．07±1．26）％、（18．29±1．14）％和（34．97±1．90）％，Bay11-7082作用后增至（60．32±3．59）％、（41．29±3．23）％和（66．49±2．96）％；联合用药后增高更为明显，分别为（104．62±5．02）％、（94．72±4．28）％和（101．59±4．04）％。不同处理方式间三者差异均有统计学意义（F=575．13、625．95和712．87，P均〈0．01），联合处理组与单独用药组比较g值15．95～86．01（P均〈0．01）�Objective To study pro-apoptotic effects of a nuclear factor-kappa B （NF-κB） inhibi- tor （ Bay 11-7082） and ^131Ⅰ on DTC cells and investigate the synergistic effects of the combined treatments. Methods Western blot was used to detect relative protein expression changes of NF-κB regulated to anti- apoptotic factors （ X-chromosome-linked inhibitor of apoptosis （XIAP） and survivin） as well as key apoptot- ic factors （caspase 3 and poly-adenosine diphosphate-ribose polymerase （PAP, P）） after either mono-treat- ment and combined treatment for 24 h. β-actin was used as control and semi-quantitative analysis was per- formed. Flow cytnmetry with Annexin V-fluoreseein isothiocyanate/propidium iodide double staining wasused to analyze the induction of apoptosis after different treatments as well. One-way analysis of variance and q test were used for statistical analysis. Results Basic expressive levels of XIAP and survivin were （ 16.62 ± 0.73） % and （ 15.20 ± 0.53 ） % , respectively. The levels increased to （95.22 ± 3.27） % and （71.80 ±2.76）% after ^131Ⅰ treatment, respectively. In the combined treatment group with ^131Ⅰ and Bay 11- 7082, XIAP and survivin expressions were （ 8.29 ± 0.35 ） % and （6.87 ± 0.28 ） %, respectively. The differences of XIAP and survivin with different treatments were statistically significant （ F = 1823.47 and 1406.12, both P 〈 0.01 ）. The expression levels in the combined treatment group showed significant differ- ences compared with that in ^131Ⅰ mono-treatment or the control group （ q = 13.37 - 45.38, all P 〈 0.01 ）. Basic levels of caspase 3 subunits p19 and p17, as well as degraded PARP protein p89 were （4.93 ± 0. 49） %, （4.67 ± 0.34） % and （4.87 ± 0.64） %, respectively. After 131i treatment they displayed ex- pressive enhancement as （25.07 ±1.26）%, （18.29 ± 1.14）% and （34.97 ± 1.90）%, and after Bay 11-7082 treatment their levels increased to （60.32 ±3.59）%, （41.29 ±3.23）% and

关 键 词：甲状腺肿瘤 细胞凋亡 碘放射性同位素 药物协同作用 BAY 11-7082 

分 类 号：R736.1[医药卫生—肿瘤]