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信号转导与转录激活因子（STATs）是一类发挥信号转导和转录因子调节作用的蛋白质家族，它们可以作为信号转导分子和转录调节因子参与到细胞因子和生长因子对于正常细胞的调控作用中。STATs 的异常激活，特别是STAT3 激活，和多种人类恶性肿瘤相关联。相关的分子生物学和药理学模型的研究也已确认STAT3在肿瘤发生中的重要作用，这些工作为抗癌药物研发和治疗癌症提供了新的靶标。此外，结构性活化的STAT3 突变体就足以诱导瘤原细胞的转化，并且进一步在体内形成肿瘤。结构性激活的STAT3 信号通路常常伴随着一些基因如cyclinD1，c-Myc 和Bcl-x 的上调，同时也会破坏正常细胞生长与生存的调控机制。体外和体内的实验研究结果也证明，对于STAT3 信号通路结构性的阻断可以导致STAT3 高表达肿瘤类型中的细胞生长抑制和凋亡。这种已被证实了的肿瘤细胞内的结构性激活和生长存活之间的相互联系，为癌症治疗提供了广阔的应用前景。近年来针对STAT3 抑制剂的研究逐渐成为热点，本文就此作一综述。

英文摘要:

Signal Transducers and Activators of Transcription (STATs) are a family of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Frequently, however, abnormal activity of certain STAT family members, particularly STAT3, is associated with a wide variety of human malignancies. Application of molecular biology and pharmacology tools in disease-relevant models has confirmed STAT3 as having a causal role in oncogenesis, and provided validation of STAT3 as a new target for cancer drug discovery and therapeutic intervention. Futhermore, a constitutively-active mutant form of STAT3 is sufficient to induce oncogenic transformation of cells, which form tumors in vivo. Constitutive activation of STAT3 signaling is accompanied by upregulation of cyclinD1, c-Myc, and Bcl-x, changes consistent with subversion of normal cellular growth and survival control mechanisms. Block of constitutive STAT3 signaling results in growth inhibition and apoptosis of STAT3-positive tumor cells in vitro and in vivo. The observed dependence of certain tumors on constitutive STAT3 signaling for growth and survival has wide implications for cancer therapy, offering the potential for preferential tumor cell killing. This article reviewed the hot research topic in development of STAT3 inhibitor.

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