Aumolertinib可体内外抑制人脉络膜黑色素瘤MUM-2B细胞的增殖  

Aumolertinib inhibits growth of human choroidal melanoma MUM-2B cells in vitro and in vivo

作　　者：李娟[1] 王爱莲[1] 李宁[1] 祝英泽 李坤 刘浩 高自清[1] LI Juan;WANG Ailian;LI Ning;ZHU Yingze;LI Kun;LIU Hao;GAO Ziqing(Department of Ophthalmology,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;School of Pharmacy,Bengbu Medical College,Bengbu 233030,China;Institute of Biomedical and Health Science,School of Life and Health Science,Anhui Science and Technology University,Fengyang 233100,China)

机构地区：[1]蚌埠医学院第一附属医院眼科,安徽蚌埠233000 [2]蚌埠医学院药学院//安徽省生化药物工程技术研究中心,安徽蚌埠233030 [3]安徽科技学院生命与健康科学学院生物医药与健康研究院,安徽凤阳233100

出　　处：《南方医科大学学报》2022年第11期1604-1610,共7页Journal of Southern Medical University

基　　金：蚌埠医学院转化医学重点专项(BYTM2019011);蚌埠医学院校级大学生创新创业训练计划项目(bydc2021074)。

摘　　要：目的评估新型第3代表皮生长因子受体酪氨酸激酶抑制剂Aumolertinib对人脉络膜黑色素瘤MUM-2B细胞增殖的影响,探索Aumolertinib在眼科肿瘤治疗中的应用潜力。方法不同浓度Aumolertinib(0、2、4、6、8、10μmol/L)处理MUM-2B细胞。用CCK-8法检测Aumolertinib对MUM-2B细胞存活率的影响;细胞集落克隆形成实验检测Aumolertinib对MUM-2B细胞的增殖抑制作用;利用流式细胞分析技术检测Aumolertinib对MUM-2B细胞凋亡坏死、线粒体膜电位、活性氧、细胞周期分布的影响;建立人脉络膜黑色素瘤细胞MUM-2B裸鼠荷瘤模型,设置空白组,给药组(40 mg/kg),考察Aumolertinib在体内的抗肿瘤活性。结果CCK-8和细胞集落克隆形成实验的结果表明,Aumolertinib显著抑制MUM-2B细胞的增殖,并呈浓度依赖性。凋亡坏死分析结果显示,当Aumolertinib浓度增加到8μmol/L时,MUM-2B细胞的总凋亡率可达到76.65%。同时,MUM-2B细胞内ROS水平也随Aumolertinib浓度增加显著增多。此外,Aumolertinib能够有效降低MUM-2B细胞的线粒体膜电位,诱导MUM-2B细胞发生G1期周期停滞。体内研究表明,Aumolertinib有效抑制肿瘤增长,而不会使动物体质量明显减轻。结论Aumolertinib对人脉络膜黑色素瘤MUM-2B细胞在体外、体内试验中均发挥有效的抗肿瘤作用,在脉络膜黑色素瘤的治疗方面具有潜在用途。Objective To investigate the inhibitory effect of aumolertinib on proliferation of human choroidal melanoma MUM-2B cells and explore the possible molecular mechanism.Methods CCK-8 assay and colony formation assay were used to evaluate the inhibitory effect of different concentrations of aumolertinib on viability and proliferation of MUM-2B cells.Flow cytometry was performed to analyze the apoptosis,necrosis,cellular ROS production and cell cycle changes in aumolertinib-treated MUM-2B cells.The antitumor effect of aumolertinib against human choroidal melanoma was observed in nude mouse models bearing MUM-2B tumor cell xenografts.Results The results of CCK-8 and colony formation assay showed that aumolertinib strongly inhibited the proliferation MUM-2B cells in a dose-dependent manner.Flow cytometry showed that aumolertinib dose-dependently increased the total apoptosis rate of MUM-2B cells to as high as 76.65%at the concentration of 8μmol/L and induced obvious cell cycle arrest at G1 phase.Aumolertinib treatment also caused a dose-dependent increase of ROS production and reduction of mitochondrial membrane potential in MUM-2B cells.In the tumor-bearing nude mice,treatment with aumolertinib significantly inhibited tumor growth without causing obvious body weight loss.Conclusion Aumolertinib can effectively inhibit the growth of human choroidal melanoma MUM-2B cells both in vivo and in vitro,suggesting its potential clinical value in the therapy of choroidal melanomas.

关 键 词：人脉络膜黑色素瘤 Aumolertinib 表皮生长因子受体 

分 类 号：R739.7[医药卫生—肿瘤]