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化学抑制剂抗癌药物调节非浸润性和浸润性乳腺癌细胞系的机械性能和细胞骨架结构:来曲唑、依西美坦和依维莫司作用的研究。

Chemical inhibitor anticancer drugs regulate mechanical properties and cytoskeletal structure of non-invasive and invasive breast cancer cell lines: Study of effects of Letrozole, Exemestane, and Everolimus.

机构信息

Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.

National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Biochem Biophys Res Commun. 2021 Aug 6;565:14-20. doi: 10.1016/j.bbrc.2021.05.083. Epub 2021 Jun 2.

Abstract

Regardless of their target and mechanism, anticancer drugs directly influence biological behavior of cancer cells by activating chemical signaling pathways. Due to the complex interaction between diverse signaling pathways, these drugs may profoundly impact the physical characteristics of cancer cells and regulate their mechanical properties. In this study, the effects of two Aromatase Inhibitor (Letrozole and Exemestane), and one mTOR Inhibitor (Everolimus) on cell mechanical properties, actin content/distribution, and nuclear areas of two invasive and non-invasive breast cancer cell line after 24 h treatment with concentrations previously reported were investigated. While metabolic activity of cell lines was highly affected by drug treatment, significant alterations in Young's modulus of cell bodies, nuclear areas, and actin content and distribution were reported with higher impact on invasive cells. It was concluded that regulation of mechanical behavior of cells by all three drugs emphasizes the cross talk between chemical and physical signaling cascades, and describes a correlation between biological and physical behaviors of cancer cells which might give an insight to a better understanding of mechanisms by which anti-cancer drugs function to enhance their performances.

摘要

无论其靶标和机制如何,抗癌药物通过激活化学信号通路直接影响癌细胞的生物行为。由于不同信号通路之间的复杂相互作用,这些药物可能会深刻影响癌细胞的物理特性并调节其机械特性。在这项研究中,研究了两种芳香酶抑制剂(来曲唑和依西美坦)和一种 mTOR 抑制剂(依维莫司)对两种侵袭性和非侵袭性乳腺癌细胞系在先前报道的浓度下处理 24 小时后细胞机械特性、肌动蛋白含量/分布和核区的影响。虽然细胞系的代谢活性受到药物治疗的高度影响,但报道了细胞体的杨氏模量、核区以及肌动蛋白含量和分布的显著变化,对侵袭性细胞的影响更大。研究结论认为,三种药物对细胞机械行为的调节强调了化学和物理信号级联之间的串扰,并描述了癌细胞的生物学和物理行为之间的相关性,这可能有助于更好地理解抗癌药物发挥作用的机制,以提高它们的性能。

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