B细胞淋巴瘤-XL在甲状腺癌组织的表达及其与凋亡抵抗的关系  

Expression of B-cell lymphoma-XL in thyroid cancer and its role in apoptosis resistance in thyroid cancer cells

作　　者：赵爱国[1] 宋华勇 王文胜[1] 董玲 张晗[1] 邱新光[3] Zhao Aiguo;Song Huayong;Wang Wensheng;Dong Ling;Zhang Han;Qiu Xinguang(Department of Thyroid Surgery,the First Affiliated Hospital of Henan University,Kaifeng 475000,China;Department of Oncology,the First Affiliated Hospital of Henan University,Kaifeng 475000,China;Department of Thyroid Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]河南大学第一附属医院甲状腺外科,开封475000 [2]河南大学第一附属医院肿瘤科,开封475000 [3]郑州大学第一附属医院甲状腺外二科,450052

出　　处：《中华实验外科杂志》2021年第8期1557-1559,共3页Chinese Journal of Experimental Surgery

基　　金：河南省高等学校重点科研项目计划支持(19B320006)。

摘　　要：目的检测B细胞淋巴瘤-XL基因(bcl-XL)在甲状腺癌组织和甲状腺癌细胞系的表达,探讨其是否参与甲状腺癌细胞的凋亡抵抗。方法采用免疫组织化学(IHC)检测2015年9月至2019年9月保存在河南大学第一附属医院的161例甲状腺癌组织中bcl-XL的表达水平,采用蛋白质印迹法(Western blot)检测其在5个甲状腺癌细胞株的蛋白表达。应用小分子bcl-XL抑制剂ABT-737处理甲状腺癌细胞,采用细胞计数试剂盒(CCK-8)方法观察对细胞活性的影响,并应用Western blot检测对凋亡信号蛋白的影响。结果bcl-XL在53%(85/161)的甲状腺癌组织有明显表达。bcl-XL的表达与原发灶大小差异无统计学意义(χ^(2)=0.785,P>0.05),与局部颈部淋巴结转移和远处转移呈正相关(χ^(2)=7.848、8.531,P<0.01)。bcl-XL在5种甲状腺癌细胞系中均有明显表达,在乳头状癌细胞系TPC-1和未分化癌细胞系HTh83表达较高。bcl-XL小分子抑制剂ABT-737处理后,呈浓度和时间依赖性抑制甲状腺癌细胞的活性,并诱导TPC-1细胞发生凋亡。Western blot检测显示ABT-737可促使凋亡关键酶半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3激活,PARP裂解。结论bcl-XL在甲状腺癌组织和甲状腺癌细胞表达普遍上调,可能是甲状腺癌细胞产生凋亡抵抗的因素之一。靶向抑制bcl-XL可激活凋亡信号,诱导甲状腺癌细胞发生凋亡,从而抑制甲状腺癌细胞生长。Objective We investigated the expression of B-cell lymphoma-XL(bcl-XL)in thyroid cancer tissue and thyroid cancer cell lines,and its role in apoptosis resistance of thyroid cancer cells.Methods Immunohistochemistry(IHC)was used to examine the expression of bcl-XL in thyroid cancer tissue.Western blotting was used to examine the expression of bcl-XL in 5 thyroid cancer cell lines.The anti-apoptotic role of bcl-XL in thyroid cancer apoptosis cells was investigated with a small molecule inhibitor ABT-737 and cell counting kit-8(CCK-8)assay in HTh83 and TPC-1 cell lines.The effect of ABT-737 on the apoptosis signaling proteins were investigated by Western blotting.Results bcl-XL was detected in 85 out of 161 thyroid cancer tissue.The level of bcl-XL expression was significantly correlated with local lymphatic or distant metastasis,but had no correlation with patients'age,gender,and the size of primary tumor.The bcl-XL was detected in all 5 thyroid cancer cell lines tested,and had the highest level in undifferentiated HTh83 and papillary cancer TPC-1 cell lines.Treatment with bcl-XL inhibitor ABT-737 resulted in cell viability inhibition,and also led to cysteinyl aspartate-specific protease(Caspase)-3 activation and PARP cleavage in TPC-1 cell line.Conclusion The bcl-XL is highly expressed in a large fraction of thyroid cancer tissue and also in most thyroid cancer cell lines.The bcl-XL represents an important factor for apoptosis resistance in thyroid cancer cells.

关 键 词：甲状腺癌 基因表达 凋亡 

分 类 号：R736.1[医药卫生—肿瘤]