Cyr61对慢性粒细胞白血病伊马替尼耐药的影响及其机制研究  

Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism

作　　者：宋艳芳[1] 罗丽 施鹏冲 李钊钟 张太刚 曹颖平[3] 祝先进[3] SONG Yan-Fang;LUO Li;SHI Peng-Chong;LI Zhao-Zhong;ZHANG Tai-Gang;CAO Ying-Ping;ZHU Xian-Jin(Scientific Research Laboratory,Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou 350004,Fujian Province,China;College of Integrated Chinese and Western Medicine of Fujian University of Traditional Chinese Medicine,Fuzhou 350108,Fujian Province,China;Department of Clinical Laboratory,Fujian Medical University Union Hospital,Fuzhou 350000,Fujian Province,China)

机构地区：[1]福建中医药大学附属人民医院科研实验室,福建福州350004 [2]福建中医药大学中西医结合学院,福建福州350108 [3]福建医科大学附属协和医院检验科,福建福州350000

出　　处：《中国实验血液学杂志》2023年第1期1-7,共7页Journal of Experimental Hematology

基　　金：福建省自然科学基金(2020J011040,2016J01569);国家自然科学基金资助项目(81700098);福建省科技创新联合资金项目(2019Y9060)。

摘　　要：目的:探讨Cyr61对慢性粒细胞白血病(CML)伊马替尼(IM)耐药的影响及相关机制。方法:采用酶联免疫吸附实验检测细胞培养上清中Cyr61含量,采用real-time PCR和Western blot检测细胞中Cyr61和Bcl-xL的表达水平,采用Annexin V-APC试剂盒分析细胞凋亡情况,通过Western blot检测细胞中信号通路相关蛋白的表达。结果:在CML IM耐药细胞系K562G细胞中Cyr61的表达水平增高。特异性下调Cyr61的表达降低了K562G细胞对IM的耐药性,促进IM诱导的细胞凋亡;在CML小鼠模型中,特异性下调Cyr61的表达能够提高K562G细胞对IM的敏感性。机制研究提示,Cyr61介导CML细胞IM耐药与Cyr61调控ERK1/2通路和凋亡相关分子Bcl-xL有关。结论:Cyr61在促进CML细胞IM耐药中起着重要作用,靶向Cyr61或其相关效应通路可能是克服CML细胞IM耐药的途径之一。Objective:To investigate the effect of Cyr61 on imatinib(IM)resistance in chronic myeloid leukemia(CML)and its mechanism.Methods:Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay.The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot.Cell apoptosis was analyzed using an Annexin V-APC Kit.Expression of signal pathways related proteins was determined by Western blot.Results:The level of Cyr61 obviously increased in K562 G cells(IM resistance to CML cell line K562).Down-regulating the expression of Cyr61 decreased the resistance of K562 G cells to IM and promoted IM induced apoptosis.In CML mouse model,down-regulating the expression of Cyr61 could increase the sensitivity of K562 G cells to IM.The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.Conclusion:Cyr61 plays an important role in promoting IM resistance of CML cells.Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.

关 键 词：慢性粒细胞白血病 富含半胱氨酸蛋白61 耐药 伊马替尼 

分 类 号：R733.72[医药卫生—肿瘤]