Aumolertinib可体内外抑制人脉络膜黑色素瘤MUM-2B细胞的增殖

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。

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

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.