蛋白激酶CK2及其抑制剂在肿瘤多药耐药中的研究进展  

The progress on protein kinase CK2 and its inhibitors in the multi-drug resistance of tumors

作　　者：凌娜[1,2] 徐贵国 高铭泽 李玮璐 汲晨锋[1,2] 王海峰[3] LING Na;XU Guiguo;GAO Mingze;LI Weilu;JI Chenfeng;WANG Haifeng(Research Center of Pharmaceutical Engineering Technology,Harbin University of Commerce,Harbin 150076,China;Engineering Research Center of Natural Anticancer Drugs,Ministry of Education,Harbin University of Commerce,Harbin 150076,China;Chinese Herbal Medicines College,Shenyang Pharmaceutical University,Shengyang 110016,China)

机构地区：[1]哈尔滨商业大学药物工程研究中心,黑龙江哈尔滨150076 [2]哈尔滨商业大学抗肿瘤天然药物教育部工程研究中心,黑龙江哈尔滨150076 [3]沈阳药科大学中药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2024年第2期258-266,273,共10页Journal of Shenyang Pharmaceutical University

基　　金：黑龙江省重点研发计划资助项目(GZ20210088);黑龙江省属高校青年创新人才资助项目(2020CX38,2020CX37)。

摘　　要：肿瘤耐药性是临床上化疗失败的主要原因之一。蛋白激酶CK2是一种高度保守、具有广泛生物学活性的丝氨酸/苏氨酸蛋白激酶,可磷酸化数百种底物。CK2的激活及过表达在肿瘤发生、发展及耐药过程中起到重要作用,并且CK2通过多种机制和信号通路参与耐药细胞中药物的外排、DNA损伤修复以及药物逃逸反应等,并调控耐药细胞中分子伴侣的活性。本研究主要对蛋白激酶CK2的结构功能及其在肿瘤多药耐药中的作用机制进行综述,并对CK2抑制剂在血液系统肿瘤、乳腺癌、胃癌、肺癌等多种实体瘤中的应用进行了探讨,为临床上开发新的肿瘤耐药分子标志物以及肿瘤的靶向治疗提供新的思路和治疗方案。Objective Tumor multidrug resistance is one of the main reasons for the failure of clinical chemotherapy.Casein kinase 2(CK2)is a highly conserved serine/threonine protein kinase with a wide range of biological activities,that phosphorylates hundreds of substrates.The activation and over-expression of CK2 play an important role in the tumor genesis,development and drug resistance.In addition,CK2 is involved in drug efflux,DNA damage repair and drug escape responses through a variety of mechanisms and signaling pathways,and regulates the activity of molecular chaperones in drug-resistant cells.In this study,the structure,function of CK2 and its mechanism in multi-drug resistance of tumors are summarized,and the CK2 inhibitors in blood system tumor,breast cancer,gastric cancer,lung cancer and other solid tumors are discussed,which will provide new ideas for the development of new molecular markers of drug resistance and treatment plan for clinical targeted therapy.

关 键 词：蛋白激酶CK2 CK2抑制剂 肿瘤 多药耐药 作用机制 

分 类 号：R73[医药卫生—肿瘤]