缺氧诱导因子-1抑制剂放射增敏作用的研究进展

Progress in radiosensitization of hypoxia-inducible factor-1 inhibitors

缺氧诱导因子-1(HIF-1)是响应瘤内缺氧的主要核转录因子,通过抑制HIF-1来改善肿瘤乏氧是最近研究的热点。HIF-1抑制剂可影响磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物西罗莫司(雷帕霉素)靶蛋白和Ras蛋白/Raf蛋白/丝裂原活化蛋白激酶激酶1-2/细胞外信号调节激酶1-2两条信号转导通路,抑制热激蛋白90功能,降低HIF-1转录活性等。HIF-1抑制剂与辐射联用后,显著增强癌细胞的放射敏感性,明显降低乏氧细胞的放疗抵抗,有利于提高肿瘤放疗的治疗效果。目前对HIF-1抑制剂作用机制的研究较多,但与辐射的联合应用研究较少,本文对HIF-1抑制剂的放射增敏作用加以综述。

Hypoxia-inducible factor-1 （HIF-1） is a main nuclear transcription factor for response to intratumor hypoxia. Recently, it has become a hot spot to attempt to improve hypoxia by inhibiting HIF-I. HIF-1 inhibitors＇ mechanisms of action are wide, which influences the two signal transduction pathways that are phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin and Ras/Raf/mitogen- activated protein kinase kinasel-2/extracellular signal-regulated kinasel-2, inhibits the function of heat shock protein 90, and reduces transcriptional activity of HIF-I. In combination with radiation, HIF-1 inhibitors significantly enhance radiosensitivity and weaken radioresistance of hypoxia cells, which contributes to the theraDeutic effect of tumor irradiation.