蛋白激酶CK2抑制剂-醌茜素在非小细胞肺癌中的抗肿瘤作用  

Anti-cancer effects of a protein kinase CK2 inhibitor quinalizarin against non-small cell lung cancer

作　　者：李珂[1] 周瑜[2,3] 张盛[2] 李倩文[2] 李振宇[2] 周方正[2] 伍钢[2] 孟睿[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院药剂科,湖北武汉430022 [2]华中科技大学同济医学院附属协和医院肿瘤中心,湖北武汉430022 [3]华中科技大学同济医学院附属同济医院核医学科,湖北武汉430022

出　　处：《中国医院药学杂志》2016年第17期1460-1465,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(蛋白激酶CK2与肿瘤放射敏感性的关系研究,编号:81101690);湖北省自然科学基金项目(金纳米载药体系在不同生物样本中摄取效率及动力学研究,编号:2014cfb403);武汉市科技局应用基础研究资助项目(CK2激酶抑制剂+HIF-1耦联纳米金在肺癌放疗增敏中的作用及其机制研究,编号:2014060101010034)

摘　　要：目的:研究蛋白激酶CK2抑制剂-醌茜素在非小细胞肺癌中的抗肿瘤作用,探讨蛋白激酶CK2成为非小细胞肺癌治疗新靶点的可能。方法:使用MTT法检测细胞增殖,研究醌茜素对非小细胞肺癌细胞A549、H460细胞增殖的影响,探究醌茜素作用于A549、H460增殖的可能途径。使用流式细胞术检测醌茜素作用于A549、H460后,细胞的凋亡以及周期的变化。使用Trans-well迁移实验检测细胞迁移能力,探究醌茜素对A549、H460迁移的影响。结果:醌茜素能够抑制A549、H460细胞的增殖,并且该抑制作用具有时间依赖性及浓度依赖性(P<0.01,P<0.01)。在25μmol·L-1及50μmol·L-1浓度下,醌茜素能够促进细胞A549、H460凋亡(P<0.01,P<0.01;P<0.01,P<0.01)。在实验条件下,醌茜素对A549的周期影响差异没有统计学意义,但醌茜素在50μmol·L-1浓度下对H460具有周期阻滞作用,G2/M期的比例明显增加(P<0.01)。醌茜素能够显著抑制A549、H460细胞的迁移活动。结论:蛋白激酶CK2抑制剂-醌茜素能够抑制非小细胞肺癌细胞系A549、H460增殖、迁移,促进其凋亡,发挥抗肿瘤作用,有可能成为一种具有潜力的非小细胞肺癌分子靶向治疗的新型药物。OBJECTIVE To explore whether quinalizarin, a specific inhibitor of protein kinase CK2, can exert anti-cancer effects on different non-small cell lung cancer cells, and investigate the potential of protein kinase CK2 to be a new therapeutic target for none small cell lung cancer. METHODS MTT assays were performed to evaluate cell viability after A549 and H460 cells were treated with quinalizarin. Flow cytometry was used to assess apoptosis rates and cell cycles after exposure to quinalizarin. Trans-well migration assays were used to explore whether quinalizarin would result in reduction of cell migration. RESULTS Compared with control group,viabilities of A549 and H460 exposed to quinalizarin were significantly suppressed in a time and dose dependent manner （P〈0. 01 ,P〈0. 01）. Apoptosis rates increased in both A549 and H460 after being treated by quinalizarin at concentrations of 25μmol·L^-1 and 50μmol· L^- 1 （p〈0. 01, P〈0. 01 ; P〈 0. 01, P〈0. 01）. Besides, quinalizarin also affected cell cycles of H460 cells with G2/M cell cycle arrest （P〈0. 01）. In addition,quinalizarin inhibited cell migrations in both A549 and H460. CONCLUSION Specific CK2 inhibitor quinalizarin can inhibit cell proliferation, suppress migration and promote apoptosis in A549 and H460 ceils. Specific CK2 inhibitor presents good antitumor effects and shows its capacity to be a new promising molecular targeted drug for treatment of non-small cell lung cancer.

关 键 词：蛋白激酶CK2 非小细胞肺癌 醌茜素 肿瘤治疗靶点 

分 类 号：R979.1[医药卫生—药品]