上皮间质转化抑制剂及其在抗肿瘤治疗中的应用

Epithelial-mesenchymal Transition(EMT)-related Inhibitors and Its Applications in Cancer Therapy

上皮细胞转化为间质细胞的过程称为上皮间质转化(epithelial-mesenchymal transition,EMT)。EMT参与调控胚胎发育、伤口愈合及干细胞分化等生命活动,是生命体中的重要生物过程。肿瘤细胞发生EMT会使自身侵袭性、抗凋亡能力及耐药性增强,有利于肿瘤细胞的局部浸润和远端转移,加快肿瘤发展进程,因此,抑制EMT发生可作为研发抗肿瘤药物的一个重要方向。EMT过程受肿瘤细胞微环境刺激因素、胞外介质及其受体、信号通路应答、转录因子以及miRNA等多因素的调控。本文针对这几个方面,总结并归纳了几类EMT抑制剂的研究及其在抗肿瘤治疗中的优缺点,并讨论了这些抑制剂作为抗肿瘤药物成功应用于临床治疗需要进一步解决的问题。

Conversion of epithelial cells into mesenchymal cells is defined as epithelial-mesenchymal transition （EMT）. EMT is considered to be an important biological process and has a potent role in regulation of embryonic development, wound healing and stem cell differentiation. After undergoing EMT, tumor cells are characterized by increased invasiveness, resistance to apoptosis and antitumor drugs, which favors their invasiveness to adherent site and further migration to distant tissues to accelerate tumor development. Therefore, EMT endows tumor cells with malignant abilities. EMT may represent a new target for antitumor drug discovery. EMT process is regulated by many factors in different levels, such as stimulus from tumor microenvironment, extracellular mediators and the corresponding receptors, intracellular signal pathways, transcription factors and microRNAs （miRNAs）. Here, we classify the compounds that target the above EMT-related factors, and highlight some compounds of particularly importance which would be addressed in depth for their clinical application.