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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

叉头盒A3（FOXA3）通过靶向转移相关的结肠癌1（MACC1）信号通路在大肠癌细胞中抑制癌症的干性并部分增强化学敏感性。

卷 21, 期 3, 2021

发表于: 07 December, 2020

页: [254 - 267] 页: 14

弟呕挨: 10.2174/1568009620666201207150632

价格: $65

Open Access Journals Promotions 2
摘要

背景：晚期结直肠癌（CRC）治疗的主要挑战是化学耐药性的持续发生。已确定的病因之一是存在癌干样细胞（CSC），因此，肿瘤表现出对外部治疗挑战的抵抗力。 目的：前叉箱A3（FOXA3）是有效的转录因子，可在许多生理系统中增强干果的获得和维持。但是，尚未在CRC中探讨其对癌症干性的影响，特别是对癌症的治疗，构成了当前研究的基础。 方法：采用RT-qPCR检测FOXA3在耐奥沙利铂的CRC组织和细胞中的表达。使用WST-1，凋亡ELISA，集落形成和异种移植模型评估了FOXA3操作对奥沙利铂敏感性的影响。使用肿瘤球分析和CD44染色确定FOXA3改变对CSC的影响。使用ChIP，Co-IP和荧光素酶报告基因分析研究了FOXA3对MACC1的转录调控。 结果：与对奥沙利铂敏感的患者的肿瘤样品相比，在非奥沙利铂无反应的患者的肿瘤样品中FOXA3表达显着降低。 FOXA3表达的这种下调预示了在我们117名患者的队列中化疗后总体或无病生存期较差。 FOXA3下调显着增强了细胞存活和干样性质，从而使CRC细胞对奥沙利铂诱导的细胞死亡无反应。从机理上讲，FOXA3的抗肿瘤作用主要是通过对奥沙利铂耐药的CRC细胞中结肠癌1（MACC1）相关转移的转录抑制进行介导的。 结论：我们的发现建立了FOXA3作为CRC中有效的肿瘤抑制因子，它可能通过抑制CRC细胞内MACC1的转录而破坏茎的维持并调节对奥沙利铂的敏感性。

关键词: 大肠癌（CRC），癌干细胞（CSC），叉头盒A3（FOXA3），转移相关的结肠癌1（MACC1），奥沙利铂，细胞凋亡。

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