文章：

复杂凋亡信号通路对癌细胞治疗敏感性的影响

Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

原文发布日期：28 February 2024

DOI: 10.3390/cancers16050984

类型: Article

开放获取: 是

英文摘要：

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, thec-Jun/activator protein 1 (AP-1)/p53signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergoc-Jun/AP-1–mediated apoptotic death and are involved inc-JunN-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of thep53genotype.Gadd153induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g.,BaxandBcl-xS) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such asBcl-2enhances anticancer drug efficacy. The modulation of apoptotic signaling byBcl-xStransduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy.

摘要翻译： 

抗癌药物可在多种癌症类型中诱导凋亡性和非凋亡性细胞死亡。研究表明，抗癌药物诱导的凋亡性细胞死亡信号通路在药物敏感细胞与耐药细胞中存在差异。在非典型多药耐药白血病细胞中，导致凋亡死亡的c-Jun/激活蛋白1(AP-1)/p53信号通路发生改变。经抗癌药物处理的癌细胞经历c-Jun/AP-1介导的凋亡死亡，该过程涉及c-Jun氨基末端激酶活化以及生长阻滞与DNA损伤诱导基因153(Gadd153)/CCAAT增强子结合蛋白同源蛋白通路诱导，且与p53基因型无关。Gadd153诱导与抗癌药物治疗后线粒体膜通透性改变相关，并涉及内质网应激反应的耦联机制。抗癌药物诱导的细胞凋亡通过内源性途径（细胞色素c，Cyt c）及促凋亡基因（如Bax和Bcl-xS）的相互作用介导，进而激活caspase级联反应。抗癌药物诱导的细胞凋亡包含caspase依赖性和非依赖性途径，通过内源性和外源性通路发生。靶向Bcl-2等抗凋亡基因可增强抗癌药物疗效。通过Bcl-xS转导调控凋亡信号通路，能提高多药耐药相关蛋白过表达的表皮样癌细胞对抗癌药物的敏感性。自噬在癌症治疗中的意义仍有待阐明。本综述系统总结了当前关于癌细胞死亡相关信号通路及其在抗癌药物治疗过程中的改变，并探讨了提升治疗效果的潜在策略。

原文链接：

Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy