生成非整倍体细胞并评估其在化疗药物作用下的存活能力。

4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology
Methods in cell biology Pub Date : 2024-01-01 Epub Date: 2022-11-24 DOI:10.1016/bs.mcb.2022.10.012
Marica Rosaria Ippolito, Stefano Santaguida
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引用次数: 0

摘要

非整倍体是指细胞的染色体数目异常,不是单倍体的倍数。众所周知,非整倍体会对细胞生理产生有害影响,如基因组不稳定、代谢和蛋白毒性压力以及细胞活力下降。重要的是,非整倍体是肿瘤的一个特征,它与化疗药物的抗药性和不良临床结果有关。为了揭示非整倍体是如何导致化疗耐药性的,我们在人类癌细胞系中诱导染色体错分离,然后用几种化疗药物处理它们,并评估化疗耐药性的出现。通过这种方法,我们发现染色体错聚的增加会通过非整倍体核型的扩大以及随后在这些应激条件下细胞存活所必需的特定非整倍体的选择来促进对化疗药物的耐药性。在此,我们介绍一种生成非整倍体细胞群并评估其对抗癌药物耐药性的方法。这一方案已经成功应用,并可进一步用于加速探索非整倍体在化疗抗性中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Generation of aneuploid cells and assessment of their ability to survive in presence of chemotherapeutic agents.

Aneuploidy is a condition in which cells have an abnormal number of chromosomes that is not a multiple of the haploid complement. It is known that aneuploidy has detrimental consequences on cell physiology, such as genome instability, metabolic and proteotoxic stress and decreased cellular fitness. Importantly, aneuploidy is a hallmark of tumors and it is associated with resistance to chemotherapeutic agents and poor clinical outcome. To shed light into how aneuploidy contributes to chemoresistance, we induced chromosome mis-segregation in human cancer cell lines, then treated them with several chemotherapeutic agents and evaluated the emergence of chemoresistance. By doing so, we found that elevation of chromosome mis-segregation promotes resistance to chemotherapeutic agents through the expansion of aneuploid karyotypes and subsequent selection of specific aneuploidies essential for cellular viability under those stressful conditions. Here, we describe a method to generate aneuploid cell populations and to evaluate their resistance to anti-cancer agents. This protocol has been already successfully employed and can be further utilized to accelerate the exploration of the role of aneuploidy in chemoresistance.

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来源期刊
Methods in cell biology
Methods in cell biology 生物-细胞生物学
CiteScore
3.10
自引率
0.00%
发文量
125
审稿时长
3 months
期刊介绍: For over fifty years, Methods in Cell Biology has helped researchers answer the question "What method should I use to study this cell biology problem?" Edited by leaders in the field, each thematic volume provides proven, state-of-art techniques, along with relevant historical background and theory, to aid researchers in efficient design and effective implementation of experimental methodologies. Over its many years of publication, Methods in Cell Biology has built up a deep library of biological methods to study model developmental organisms, organelles and cell systems, as well as comprehensive coverage of microscopy and other analytical approaches.
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