蛋白激酶CK2抑制剂对非小细胞肺癌生长迁移及表皮生长因子受体酪氨酸激酶抑制剂靶向治疗的影响  

Effect of protein kinase CK2 inhibitor on cell viability and migration of non - small lung cancer cells and its enhanced role in sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors

作　　者：李倩雯[1] 周瑜[1] 李珂[2] 李俊玉[1] 张盛[1] 周方正[1] 董佑红[1] 伍钢[1] 孟睿[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院肿瘤中心,武汉430023 [2]华中科技大学同济医学院附属协和医院药剂科,武汉430023

出　　处：《中华实验外科杂志》2015年第8期1772-1774,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金青年基金资助项目（81101690）;武汉市科技局应用基础研究资助项目（2014060101010034）;湖北省自然科学基金资助项目（2014cfb403）

摘　　要：目的观察蛋白激酶CK2抑制剂对人类非小细胞肺癌细胞活力及迁移能力的影响及对提皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）埃克替尼（icotinib）的靶向增敏作用。方法通过Westernblot法检测蛋白激酶CK2各亚基在不同类型肺癌细胞株中的表达状态；免疫组织化学法检测CK2功能亚基在不同类型肺癌标本中得表达；采用噻唑蓝（MTT）法检测不同浓度梯度蛋白激酶CK2抑制剂醌茜素（Quinalizarin）对A549及H460细胞活力的影响；同时用Transwell迁移实验检测其对这两种细胞迁移能力的影响；通过MTT法检测醌茜素与埃克替尼联合应用对不同EGFR大达状态的非小细胞肺癌细胞活力的影响。结果通过检测蛋白激酶CK2在不同类型肺癌细胞株埂肺癌标本中的表达，发现该激酶广泛表达于各类型肺癌中。使用0、12．5、25．0、50．0μmol／L终质量浓度的醌茜素抑制激酶活性后，MTT实验检测发现，随浓度增高A549及H460细胞活力均有明显抑制（P〈0．01）；迁移实验中，随浓度增高A549细胞穿过人工基底膜的细胞数分别为（1041．0±115．9）、（705．3±74．7）、（451．3±55．0）、（128．3±38．0）个，H460穿过人工基底膜的细胞数分别为（924．0±65．6）、（593．7±69．2）、（954．7±24．7）、（193．0±27．2）个，均明显减少（P〈0．01）。埃克卡午圯与醌茜素联合应HJ分别处理A549、H1650、H1975、PC9细胞，与单独使用埃克替尼比较，存50．0、100．0μmol／L浓度时，各细胞株细胞活力明显下降（P〈0．01）。结论蛋白激酶CK2在各种类型肺癌中广泛表达，通过降低CK2的激酶活性可明显抑制非小细胞肺癌细胞活力及迁移能力，并可增强埃克替尼对不同EGFR表达状态的非小细胞肺癌细胞的抑制作用。Objective To explore the effect of the protein kinase CK2 inhibitor on cell viability and migration of human non - small lung cancer cells and its enhanced role in sensitivity to Icotinib, one of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR -TKIs）. Methods The protein expres- sion of individual CK2 subunits in different lung cancer cells was measured by Western blotting. The protein expression of the catalytic subunit - CK2α in different types of lung cancer tissues was detected by immuuohistochemistry. Methyl thiazol tetrazolium （MTT） assays and Transwell migration assays were applied to assess the effect of CK2 inhibitor Quinalizarin on cell viability and migration capabilities of A549 and H460 respectively. The effect of the combination of Icotinib and Quinalizarin on cell viability of non - small lung cancer cell lines in the presence or absence of EGFR mutation was examined by MTT assays. Results Western bolting and immunohistoehemistry revealed that protein kinase CK2 was overexpressed in different types of lung cancer cells and tissues. Quinalizarin, a CK2 inhibitor, could inhibit the cell viability of A549 and H460 cells in a dose - dependent manner within the range between 12.5 and 50. 0 μmol/L （P 〈 0. 01 ）. Along with the increased concentration of Quinalizarin, the migration of A549 and H460 was signif-icantly suppressed （ 1 041.0 -＋ 115.9, 705.3 ± 74.7, 451.3 ± 55.0, 128. 3 ± 38. 0 and 924. 0 ± 65.6, 593.7 ± 69. 2, 954.7 ± 24. 7, 193.0 ± 27.2, P 〈 0.01 ）. The combination of Ieotinib and Quinalizarin could inhibit the cell viability of A549, H1650, H1975 and PC9 as compared with Icotinib used alone in the concentrations of 50 and 100 p^mol/L （ P 〈 0.01 ）. Conclusion Protein kinase CK2 was overexpressed in different types of lung cancer. Quinalizarin, one of the CK2 inhibitors can suppress the cell viability and migration capabilities of different types of lung cancer cells. It can also enhance the effect of Icotinib on cell viability of non - sm

关 键 词：非小细胞肺癌 蛋白激酶CK2 醌茜素 埃克替尼 

分 类 号：R979.1[医药卫生—药品]