研究动态
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通过原子力显微镜研究肺癌靶向药物对心肌细胞的影响。

Effects of targeted lung cancer drugs on cardiomyocytes studied by atomic force microscopy.

发表日期:2023 Aug 11
作者: Can Cheng, Shuwei Wang, Jianjun Dong, Shengli Zhang, Dongliang Yu, Zuobin Wang
来源: Cellular & Molecular Immunology

摘要:

表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)已成为非小细胞肺癌(NSCLC)治疗的重要靶向药物之一。然而,与EGFR-TKI治疗相关的心脏不良事件(AEs)频繁发生,TKI相关心脏AEs的病例仍不被充分理解。为了研究EGFR-TKI对心肌细胞的影响,采用原子力显微镜(AFM)测量并分析了在三种具有不同浓度的药物(吉非替尼、阿法替尼和奥西替尼)作用下心肌细胞的物理特性。通过比较细胞高度、粘附力、杨氏模量、收缩和舒张过程的振幅和时间,发现细胞力学性质的变化与AEs症状(如心肌细胞肥大、QT间期延长、心房颤动、射血分数降低和心衰)具有良好的相关性。此外,在低浓度下奥西替尼对心肌细胞的影响最为明显,随着浓度的增加,吉非替尼的影响最大,而阿法替尼对心肌细胞的影响最小。这为在细胞水平上筛选药物和探讨癌症治疗过程中的作用原理提供了一种新方法。
The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has become one of the important targeted drugs for the treatment of non-small cell lung cancer (NSCLC). But the cardiac adverse events (AEs) related to the EGFR-TKI treatment occur frequently. And the cases of TKI-associated cardiac AEs remain poorly understood. In order to study the effects of EGFR-TKIs on cardiomyocytes, atomic force microscopy (AFM) was used to measure and analyze the physical properties of cardiomyocytes under the actions of three drugs (gefitinib, afatinib and osimertinib) with different concentrations. By comparing the height, adhesion, Young's modulus, the amplitude and the time of the contraction and relaxation process, it was found that the changes of the mechanical properties of cells were well correlated with the symptoms of AEs, such as cardiomyocyte hypertrophy, QT prolongation, atrial fibrillation, ejection fraction reductions, and cardiac failure. In addition, osimertinib has the most obvious effect on cardiomyocytes at a low concentration, and gefitinib has the greatest effect with the increase of concentration, while afatinib has the least effect on cardiomyocytes. This provides a new method for screening drugs and exploring the principle of action in the process of cancer treatment at the cellular level.