摘要
肿瘤细胞对化疗药物产生交叉耐药性,是造成肿瘤患者化疗失败的主要原因之一。肿瘤细胞具有异质性,即在同一肿瘤细胞中存在不同基因型或亚型的细胞。在化疗过程中,药物杀死对药物敏感的肿瘤细胞,而有一部分肿瘤细胞则表现出较强的耐药性,不能被化疗药物杀伤。肿瘤干细胞(Cancer stem cells,CSCs)的发现,为肿瘤耐药现象的研究提供了新的思路。CSCs是指肿瘤中具有自我更新能力并能产生异质性肿瘤细胞的细胞,其具有自我更新,多向分化,DNA修复以及耐药等特征。Wnt信号通路是调控肿瘤干细胞自我更新和分化的关键信号途径,该通路的激活在多种肿瘤的发生、发展和耐药过程中发挥重要作用。对Wnt信号通路的研究有助于揭示肿瘤干细胞耐药的机制,并有望成为治疗恶性肿瘤的一个新靶点。该综述重点阐述了Wnt信号通路在肿瘤干细胞介导的耐药过程中的研究进展。
Multidrug resistance,the principal mechanism by which many cancers develop resistance to chemotherapy drugs,is the single most important reason for treatment failure in cancer patients. It affects patients with a variety of blood cancers and solid tumors,including breast,ovarian,lung,and others. Tumors usually consist of mixed populations of malignant cells,some of which are drug-sensitive while others are drug-resistant. Chemotherapy kills drug-sensitive cells,but leaves behind a higher proportion of drugresistant cells. Recent evidence has emerged to supporting the hypothesis that many types of tumors contain a sub-population of cancer cells that possess characteristics normally associated with stem cells. Cancer stem cells are defined as those cells within a tumour that can self-renew and drive tumoregenesis. Cancer stem cells have the abilities of self-renewal,differentiation,DNA self-repair activity and anti-apoptosis. Cancer stem cells are the source of recurrence and may be associated with drug resistance. The Wnt signalling pathway is an important developmental pathway,which is frequently dysregulated in human cancers. Wnt signalling is important for cell migration,invasion,adhesion and survival. Wnt ligands primarily signal via membrane bound Frizzled receptors through a number of different but interconnected signalling pathways,including the Wnt / Ca2 +,Wnt/β-catenin and Wnt/planar-cell polarity pathways. Wnt signalling,a key pathway involved in various aspects of embryonic development,also underlies many human diseases,in particular,cancer. Wnt pathway has been identified as one of the key signaling pathways in cancer,which is critical in self-renewal and differentiation of tumor stem cells,and its abnormal activation leads to oncogenesis,prognosis and drug-resistant in tumor cells. Research on the Wnt signaling pathway contributes to reveal the mechanism of drug-resistant in CSCs,and the Wnt signaling pathway may become a new target for the treatment of malignant tumors. This review highlights the ro
出处
《药物生物技术》
CAS
2015年第2期165-169,共5页
Pharmaceutical Biotechnology
