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叉头框蛋白作为肿瘤细胞顺铂反应的关键调节因子。

Forkhead box proteins as the critical regulators of cisplatin response in tumor cells.

机构信息

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Eur J Pharmacol. 2023 Oct 5;956:175937. doi: 10.1016/j.ejphar.2023.175937. Epub 2023 Aug 2.

DOI:10.1016/j.ejphar.2023.175937
PMID:37541368
Abstract

Cisplatin (CDDP) is one of the most common chemotherapy drugs used in a wide range of cancer patients; however, there is a high rate of CDDP resistance among cancer patients. Considering the side effects of cisplatin in normal tissues, it is necessary to predict the CDDP response in cancer patients. Therefore, identifying the molecular mechanisms involved in CDDP resistance can help to introduce the prognostic markers. Several molecular mechanisms such as apoptosis inhibition, drug efflux, drug detoxification, and increased DNA repair are involved in CDDP resistance. Regarding the key role of transcription factors in regulation of many cellular processes related to drug resistance, in the present review, we discussed the role of Forkhead box (FOX) protein family in CDDP response. It has been reported that FOX proteins mainly promote CDDP resistance through the regulation of DNA repair, autophagy, epithelial-mesenchymal transition (EMT), and signaling pathways. Therefore, FOX proteins can be introduced as the prognostic markers to predict CDDP response in cancer patients. In addition, considering that oncogenic role of FOX proteins, the CDDP treatment along with FOX inhibition can be used as a therapeutic strategy in cancer patients.

摘要

顺铂(CDDP)是广泛应用于多种癌症患者的最常用化疗药物之一;然而,癌症患者中 CDDP 耐药率很高。鉴于顺铂在正常组织中的副作用,有必要预测癌症患者对 CDDP 的反应。因此,确定与 CDDP 耐药性相关的分子机制有助于引入预后标志物。几种分子机制,如凋亡抑制、药物外排、药物解毒和增加 DNA 修复,参与了 CDDP 耐药性。鉴于转录因子在调节与耐药性相关的许多细胞过程中的关键作用,在本综述中,我们讨论了叉头框(FOX)蛋白家族在 CDDP 反应中的作用。据报道,FOX 蛋白主要通过调节 DNA 修复、自噬、上皮-间充质转化(EMT)和信号通路来促进 CDDP 耐药性。因此,FOX 蛋白可以作为预后标志物,预测癌症患者对 CDDP 的反应。此外,考虑到 FOX 蛋白的致癌作用,CDDP 治疗联合 FOX 抑制可作为癌症患者的治疗策略。

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