缺氧诱导因子-1抑制剂放射增敏作用的研究进展

摘要

Hypoxia-inducibIe factor-1(HIF-1)is a main nucIear transcription factor for response to intratumor hypoxia. RecentIy,it has become a hot spot to attempt to improve hypoxia by inhibiting HIF-1. HIF-1 inhibitors' mechanisms of action are wide,which infIuences the two signaI transduction pathways that are phosphatidyIinositoI-3-kinase/ protein kinase B/ mammaIian target of rapamycin and Ras/ Raf/ mitogen-activated protein kinase kinase1-2/ extraceIIuIar signaI-reguIated kinase1-2,inhibits the function of heat shock protein 90,and reduces transcriptionaI activity of HIF-1. In combination with radiation,HIF-1 inhibi-tors significantIy enhance radiosensitivity and weaken radioresistance of hypoxia ceIIs,which contributes to the therapeutic effect of tumor irradiation.%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。