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机构地区:[1]徐州医学院附属连云港医院肿瘤放疗科,江苏省连云港市222002 [2]江苏省连云港市第一人民医院肿瘤放疗科
出 处:《中国肿瘤临床》2015年第10期535-539,共5页Chinese Journal of Clinical Oncology
基 金:国家自然科学基金项目(编号:81472792)资助~~
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D1(Cyclin D1)表达,使细胞周期由G1期快速进入S期,促进细胞增殖,且Cyclin D1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。Signal transducer and activator of transcription 3 (STAT3) is an important member of the STAT family of signaling pro- teins. STAT3 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-lct (HIF-1α), thus producing radio- therapy tolerance. Moreover, STAT3 can directly or by HIF-lct indirectly regulate CyclinD1 expression, thus rapidly promoting cell pro- gression through G1 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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