In Vitro Modeling of the Antitumor Drugs Effects on the Endothelial Barrier Function

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Aleksandra S. Churkina, Kseniya N. Sedenkova, Polina А. Kovaleva, Anton S. Shakhov, Anatoly A. Kotlobay, Elena B. Averina, Irina B. Alieva
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引用次数: 0

Abstract

Pulmonary edema and acute respiratory failure, developing due to the vascular endothelium dysfunction, are common side effects of anticancer therapy. This study is the first approach to create an in vitro model system to estimate vascular response at the drug development/improvement stage and to determine whether it is possible to select an antitumor drug dose effectively suppressing malignant cells without a pathological effect on the endothelial cells function. In this study (1) the doses of several clinically used antitumor drugs suppressing the common tumor cell proliferation were determined experimentally; (2) the endothelial cell viability after exposure to selected doses of these drugs was assessed in vitro; (3) changes in the endothelial monolayer condition, as well as cultured endothelial cell reactions and intracellular disorders accompanying the effects of selected drugs doses were studied in vitro using the intravital observations and super-resolution microscopy methods. This approach allowed to select antitumor drug concentrations inhibiting cell proliferation in selected tumor lines, but having no critical effect on the viability of endothelial cells and their cytoskeletal structures. As the result, an in vitro model system for studying the side effects of medications on vascular permeability was created.

抗肿瘤药物对内皮屏障功能影响的体外模型研究。
肺水肿和急性呼吸衰竭是由血管内皮功能障碍引起的,是抗癌治疗常见的副作用。本研究首次建立了体外模型系统来评估药物开发/改进阶段的血管反应,并确定是否有可能选择一种有效抑制恶性细胞而不影响内皮细胞功能的抗肿瘤药物剂量。本研究(1)通过实验确定几种临床常用抗肿瘤药物抑制常见肿瘤细胞增殖的剂量;(2)在体外评估暴露于选定剂量的这些药物后内皮细胞的活力;(3)采用活体观察和超分辨显微镜方法,研究了不同剂量药物作用下内皮单层状态的变化,以及培养内皮细胞的反应和细胞内紊乱。这种方法可以在选定的肿瘤细胞系中选择抑制细胞增殖的抗肿瘤药物浓度,但对内皮细胞及其细胞骨架结构的活力没有关键影响。因此,我们建立了一个体外模型系统来研究药物对血管通透性的副作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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