南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (11): 1604-1610.doi: 10.12122/j.issn.1673-4254.2022.11.03

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Aumolertinib可体内外抑制人脉络膜黑色素瘤MUM-2B细胞的增殖

李 娟，王爱莲，李 宁，祝英泽，李 坤，刘 浩，高自清   

  1. 蚌埠医学院第一附属医院眼科，安徽 蚌埠 233000；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；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
  • 出版日期:2022-11-20 发布日期:2022-11-30

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

LI Juan, WANG Ailian, LI Ning, ZHU Yingze, LI Kun, LIU Hao, GAO Ziqing   

  1. 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
  • Online:2022-11-20 Published:2022-11-30

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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、10 μmol/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8 μmol/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。

关键词: 人脉络膜黑色素瘤；Aumolertinib；表皮生长因子受体

Abstract: 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 8 μmol/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.

Key words: human choroidal melanoma; aumolertinib; epidermal growth factor receptor