紫杉醇微球、多柔比星微球联合应用的细胞毒性评价  

Cytotoxicity of paclitaxel microspheres combined with doxorubicin microspheres

作　　者：郝文艳 刘一婧 朱思庆 庞璐璐 马金秋 邱海莹 杜丽娜 HAO Wen-yan;LIU Yi-jing;ZHU Si-qing;PANG Lu-lu;MA Jin-qiu;QIU Hai-ying;DU Li-na(Department of Pharmaceutical Sciences,Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Anhui Medical University,Hefei 230032,China)

机构地区：[1]军事科学院军事医学研究院辐射医学研究所,北京100850 [2]山东中医药大学,济南250355 [3]安徽医科大学,合肥230032

出　　处：《国际药学研究杂志》2020年第11期975-981,共7页Journal of International Pharmaceutical Research

摘　　要：目的制备紫杉醇(PTX)、多柔比星(DOX)微球,并考察PTX微球、DOX微球联合(PTX微球&DOX微球)抑制乳腺癌细胞的增殖与转移作用,探讨其促细胞凋亡的机制。方法首先采用CCK-8法评价PTX微球&DOX微球是否具有协同作用。以小鼠乳腺癌4T1-luc细胞为模型,考察PTX微球&DOX微球的细胞毒作用。采用划痕实验考察二者对4T1-luc细胞的迁移抑制作用;采用流式细胞术考察二者促进4T1-luc细胞凋亡作用;通过细胞吞噬实验考察4T1-luc细胞对PTX和DOX微球的吞噬作用。结果与原料药组相比,PTX微球和、DOX微球对4T1-luc细胞抑制作用更为明显(P<0.01),二者对4T1-luc的IC50值分别为261.3和331.3 nmol/L,抑制作用呈剂量依赖性。PTX微球&DOX微球组对4T1-luc细胞迁移的抑制效果优于PTX&DOX组(P<0.01);DOX微球比游离DOX更易被4T1-luc细胞摄取而发挥细胞毒作用;PTX微球&DOX微球组促进4T1-luc细胞凋亡效果优于PTX&DOX组(P<0.01)。结论与PTX&DOX相比,PTX微球&DOX微球对4T1-luc细胞增殖抑制作用显著,能有效抑制乳腺癌细胞的迁移,促细胞凋亡作用明显。Objective To investigate the inhibitory effect of paclitaxel microspheres(PTX)combined with doxorubicin(DOX)microspheres(PTX microspheres&DOX microspheres)on the proliferation and metastasis of breast cancer cells,and explore the apoptosis inducing mechanism.Methods The cytotoxicity of PTX and DOX microspheres was investigated by the CCK-8 method using fluorescently labeled mouse breast cancer cells(4T1-luc).The combination effects of PTX microspheres&DOX microspheres were evaluated by the Compusyn software.The scratch test was used to investigate the inhibitory effects of PTX microspheres&DOX microspheres on migration of 4T1-luc cells.Flow cytometry was used to investigate the effect of PTX microspheres&DOX micro⁃spheres on the apoptosis of 4T1-luc cells.Cell phagocytosis assay was performed using a laser confocal microscopy to investigate the ability of 4T1-luc cells swallowing DOX and DOX microspheres.Results For 4T1-luc cells,the IC50 of PTX microspheres and DOX microspheres was 261.3 and 331.3 nmol/L,respectively.The inhibitory effect was dose-dependent,and the microsphere groups had better inhibitory effect than free drugs(P<0.05).Moreover,PTX microspheres and DOX microspheres had better inhibitory effects on the migration of cancer cells than free PTX and DOX.DOX microspheres were more easily phagocytosed by 4T1-luc cells than free DOX.Flow cytometry assay showed that PTX microspheres and DOX microspheres could promote the 4T1-luc cell apoptosis,which was better than free PTX or DOX.Conclusion Compared with the two free drug PTX and DOX combination,the combination of the PTX and DOX microspheres could significantly inhibit both the proliferation(P<0.01)and the migration of breast cancer 4T1-luc cells and showed a significant effect on promoting the apoptosis in 4T1-luc cells.

关 键 词：紫杉醇 多柔比星 微球 乳腺癌4T1-luc细胞 联合用药 

分 类 号：R992[医药卫生—毒理学]