紫杉醇治疗肺癌细胞中去泛素化酶的表达模式

IF 3.1 3区 生物学 Q3 CELL BIOLOGY
Hwa-Yeong Kim, Hae-Seul Choi, Kwang-Hyun Baek
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引用次数: 0

摘要

肺癌仍然是癌症相关死亡的主要原因,强调迫切需要更有效的治疗策略,特别是由于耐药的频繁发展。紫杉醇是一种广泛应用于非小细胞肺癌(NSCLC)的化疗药物,经常面临耐药性,限制了其临床疗效。因此,确定调节紫杉醇反应的分子标记是至关重要的。泛素-蛋白酶体系统(UPS)调节蛋白质稳态,在癌症进展、细胞凋亡和耐药性中发挥作用,而去泛素化酶(DUBs)是关键的调节因子。最近的研究表明,靶向特异性dub可能会增强药物敏感性。本研究旨在探讨DUB基因在紫杉醇治疗后的表达模式。多重RT-PCR和RT-qPCR分析显示,在紫杉醇处理的A549细胞中,USP1、USP5、USP28和USP34下调,而USP10和USP36上调。Western blot分析证实,除USP10和USP36外,所有DUBs的蛋白水平变化与mRNA表达一致,两者表现出不一致的模式。此外,通过凋亡和抗凋亡蛋白水平的改变,包括PARP、caspase-3、Bax、Bcl-2、Bcl-XL和p53,证实了紫杉醇诱导的细胞凋亡。这些DUB基因的发现凸显了它们作为预测紫杉醇治疗期间药物反应性和预后的生物标志物的潜力,从而为提高紫杉醇治疗NSCLC的疗效提出了新的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expression Patterns of Deubiquitinating Enzymes in Paclitaxel-Treated Lung Cancer Cells.

Lung cancer remains a leading cause of cancer-related mortality, underscoring the urgent need for more effective therapeutic strategies, particularly due to the frequent development of drug resistance. Paclitaxel, a widely used chemotherapeutic agent for non-small cell lung cancer (NSCLC), often faces resistance that limits its clinical efficacy. Therefore, identifying molecular markers that modulate paclitaxel responsiveness is critical. The ubiquitin-proteasome system (UPS), which regulates protein homeostasis, plays a role in cancer progression, apoptosis, and drug resistance, with deubiquitinating enzymes (DUBs), serving as key regulators. Recent studies suggest that targeting specific DUBs may enhance drug sensitivity. This study aimed to investigate the expression patterns of DUB genes in response to paclitaxel treatment. Multiplex RT-PCR and RT-qPCR analysis revealed that USP1, USP5, USP28, and USP34 were downregulated, whereas USP10 and USP36 were upregulated in paclitaxel-treated A549 cells. Western blot analysis confirmed changes in protein levels consistent with mRNA expression for all DUBs except USP10 and USP36, which displayed discordant patterns. Furthermore, paclitaxel-induced apoptosis was verified by altered levels of apoptotic and antiapoptotic proteins including PARP, caspase-3, Bax, Bcl-2, Bcl-XL, and p53. The identification of these DUB genes highlights their potential as biomarkers for predicting drug responsiveness and prognosis during paclitaxel treatment, thereby proposing a new direction for improving the therapeutic efficacy of paclitaxel in NSCLC.

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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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