Rapid screening of multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis.
Rapid screening of multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis.
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DOI：
10.1016/j.aca.2018.09.015
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发表时间：
2019-01
影响因子：
6.2
通讯作者：
Ruijun Wu;Chen Li;Cong Li;Jinyu Ren;Xiaozhi Sun;Sufang Zhang;Juncheng Zou;Xiaomei Ling
中科院分区：
文献类型：
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作者：
Ruijun Wu;Chen Li;Cong Li;Jinyu Ren;Xiaozhi Sun;Sufang Zhang;Juncheng Zou;Xiaomei Ling
鉴于肿瘤细胞/组织比受体过表达细胞的靶点种类多，肿瘤组织能更好地模拟TME，我们建立了一种在接近肿瘤生理环境下，利用非固定化肿瘤细胞/组织毛细管电泳法筛选多靶点抗肿瘤药物的新方法。在这种方法中，不需要分离和纯化就可以很好地保持肿瘤细胞/组织上靶蛋白的自然结构和活性构象。因此，我们通过一系列实验条件的优化，成功地利用该方法研究了艾迪注射液及其主要成分与肿瘤细胞/组织的相互作用，发现了7种与A549 细胞具有结合活性的成分，其中5种与肿瘤组织具有特异性相互作用，并计算了结合动力学参数(K，ka，kd，k‘)。然后，进行了体外和体内的抗肿瘤活性试验，以寻找靶向性更高、药效更好、毒副作用更低的新药物组合。最后，进行了分子对接研究，以探讨有效药物组合与A549 细胞/组织相互作用的潜在靶群。综上所述，验证了该方法的有效性和可行性，并可方便地转移到毛细管阵列电泳法进行高通量药物筛选。
As there are more target categories on tumor cells/tissues than on receptor-overexpressing cells, and tumor tissues can better simulate TME, we established a new method of screening multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis under approximately tumor physiological environment. In this method, the natural structure and active conformation of the target proteins on tumor cells/tissues can be well maintained without separation and purification. Therefore, we successfully used this method to study the interactions between the Aidi injection (ADI)/its main components and tumor cells/tissues by optimizing a series of experimental conditions, discovered seven components with binding activity to A549 cells, five of them with specific interaction to tumor tissues, and calculated the binding kinetic parameters (K,ka,kd, andk’). Then, antitumor activity assays in vitro and in vivo were carried out to discover a new drug combination with higher targeting, better pharmaceutical efficacy, and lower toxic side effects. Finally, molecular docking studies were performed to investigate the potential target groups of the interactions between the effective drug combination and A549 cells/tissues. In summary, the method was verified to be valid and feasible, and can be easily transferred to a capillary array electrophoresis for high-throughput drug screening.