一组化疗耐药膀胱癌细胞系对顺铂、长春碱和吉西他滨的不同适应策略

IF 4.6 Q1 ONCOLOGY
癌症耐药(英文) Pub Date : 2025-09-12 eCollection Date: 2025-01-01 DOI:10.20517/cdr.2025.95
Monika Cuprych-Belter, Agnieszka Łupicka-Słowik, Artur Anisiewicz, Martin Michaelis, Jindrich Cinatl, Mateusz Psurski
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引用次数: 0

摘要

目的:膀胱癌(UBC)经常发生化疗耐药,降低治疗效果。本研究旨在通过建立和表征对常见化疗药物耐药的UBC细胞系的综合小组来研究获得性耐药的多种分子机制。方法:对15个UBC细胞系进行检测:3个亲本细胞系(RT-112, TCC-SUP, UMUC-3)和12个衍生亚系适应顺铂、长春碱或吉西他滨。采用SRB法评估药物敏感性。通过实时荧光定量PCR(靶向基因包括ABCB1、dCK、hENT1、ECHDC1、TUBB3)、Western blotting(评估蛋白如p21、Cyclin B和Mcl-1)以及谷胱甘肽水平和氧化还原状态的生化评估来探索耐药机制。结果:适应亚毒株表现出明显的耐药特征和交叉耐药模式。基因表达和蛋白质分析揭示了药物和谱系特异性改变,包括p21、细胞周期蛋白B和Mcl-1等因子。谷胱甘肽代谢的变化也与耐药性有关。值得注意的是,没有一个单一的、通用的机制可以解释整个小组的阻力。结论:UBC细胞发展出多样化的、环境依赖的适应策略来抵抗顺铂、长春碱和吉西他滨。这些发现突出了化学耐药机制的复杂性。这一特征细胞系组为未来旨在了解和克服膀胱癌耐药的研究提供了宝贵的资源,表明个性化治疗方法可能是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct adaptive strategies to cisplatin, vinblastine and gemcitabine in a panel of chemoresistant bladder cancer cell lines.

Aim: Urinary bladder cancer (UBC) often develops chemoresistance, reducing treatment effectiveness. This study aimed to investigate diverse molecular mechanisms underlying acquired resistance by establishing and characterizing a comprehensive panel of UBC cell lines resistant to common chemotherapeutics. Methods: Fifteen UBC cell lines were examined: three parental lines (RT-112, TCC-SUP, UMUC-3) and twelve derived sublines adapted to cisplatin, vinblastine, or gemcitabine. Drug sensitivity was assessed using the SRB assay. Resistance mechanisms were explored via quantitative real-time PCR (targeting genes including ABCB1, dCK, hENT1, ECHDC1, TUBB3), Western blotting (assessing proteins such as p21, Cyclin B, and Mcl-1), and biochemical assessment of glutathione levels and redox state. Results: The adapted sublines exhibited distinct resistance profiles and cross-resistance patterns. Gene expression and protein analyses revealed drug- and lineage-specific alterations, involving factors such as p21, Cyclin B, and Mcl-1. Changes in glutathione metabolism were also associated with resistance. Notably, no single, universal mechanism accounted for resistance across the entire panel. Conclusion: UBC cells develop diverse, context-dependent adaptive strategies to resist cisplatin, vinblastine, and gemcitabine. These findings highlight the complexity of chemoresistance mechanisms. The characterized cell line panel represents a valuable resource for future studies aimed at understanding and overcoming drug resistance in bladder cancer, suggesting that personalized therapeutic approaches may be necessary.

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