STAT3 表达与肿瘤血管生成及放射敏感性关系的研究进展*

Role of STAT 3 in tumor angiogenesis and radiation sensitivity

  • 摘要: 信号转导和转录活化因子3(STAT3)属于STATs 家族中重要一员,广泛表达于不同类型的细胞和组织中,并参与细胞生长、增殖、凋亡、恶性转化等生理和病理过程的调控。近年来,STAT3 在肿瘤血管生成及放疗敏感性方面的研究日益增多。研究表明STAT3 活化后,一方面通过直接调控血管内皮生长因子(VEGF)表达促进血管生成进而产生放疗抗拒;另一方面STAT3 通过活化缺氧诱导因子- 1α(HIF-1α)间接促进血管生成产生放疗耐受。此外,STAT3 还可以直接或通过HIF-1α 间接调控细胞周期蛋白D 1(CyclinD1)表达,使细胞周期由G 1 期快速进入S 期,促进细胞增殖,且CyclinD1 与放疗敏感性相关。由此发现,STAT3 通过直接和间接两种途径在肿瘤血管生成及放疗抗拒方面发挥作用。本文拟对此方面的相关研究新进展作一综述。

     

    Abstract: Signal transducer and activator of transcription 3 (STAT 3) is an important member of the STAT family of signaling pro -teins. STAT 3 is widely expressed in different types of cells and tissues and is involved in many physiological and pathological process -es, including cell growth, proliferation, apoptosis, and malignant transformation. Over recent years, increased attention has been given on the role of STAT3 in tumor angiogenesis and radiation sensitivity. Studies show that on the one hand, following activation, STAT3 promotes angiogenesis by directly regulating the expression of vascular endothelial growth factor and then causes radiation resistance. On the other hand, STAT3 indirectly promotes angiogenesis by activating hypoxia-inducible factor- 1α (HIF-1α ), thus producing radio-therapy tolerance. Moreover, STAT3 can directly or by HIF-1α indirectly regulate CyclinD 1 expression, thus rapidly promoting cell pro-gression through G 1 into the S phase of the cell cycle and enhancing cell proliferation. In addition to regulating the cell cycle, CyclinD1 plays a key role in radiation sensitivity. Results suggest that STAT3 plays a role in tumor angiogenesis and radiation resistance via di -rect and indirect mechanisms. In this review, we summarize recent research advances on the role of STAT3 in regulating tumor angio -genesis and radiation sensitivity.

     

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