实体瘤细胞中低氧诱导因子-1蛋白的活性调控

Regulation of HIF-1 activity in tumor cells

实体肿瘤内部广泛存在着缺氧现象,缺氧与肿瘤的远处转移、不良预后以及放化疗的耐受性关系密切.低氧诱导因子-1(HIF-1)在细胞缺氧信号途径中处于核心位置,它能增强细胞在缺氧环境下的生存能力,促进血管的增生及肿瘤的恶性转化.HIF-1所起的核心作用使其成为治疗人类恶性肿瘤时一个非常好的靶点.HIF-1在体内的调控途径异常复杂,主要有氧浓度、葡萄糖代谢途径、原癌基因和抑癌基因的突变、PI3K-MAPK-mTOR通路、自由基以及抗氧化剂等,其中研究最透彻的是氧浓度的调节.而近年来自由基、DNA的突变以及葡萄糖代谢的调节成为研究的热点.本文将围绕近年来这几方面的研究进展进行一个综合的回顾,这将有助于针对HIF-1这一重要靶点进行抗肿瘤药物的研究.

Hypoxia regions, which have been demonstrated to widely exist in various solid tumors, are associated with remote metastasis, bad prognosis and resistance to radiation and chemotherapy. Hypoxia-inducible factor-l（HIF-1） plays a crucial role in the hypoxia signaling pathway. It not only increases the viability of tumor cells under the hypoxia condition, but also stimulates angiogenesis and malignant transformation. Therefore, HIF-1 is regarded as a very attractive target in cancer treat- ment. The regulating pathways of HIF-1 are extremely complex, including oxygen concentration, glucose metabolism, mutations in proto-oncogenes and cancer suppressor genes, the PI3K-MAPK -mTOR signaling pathway, free radicals, antioxidants, etc. The regulation of oxygen concentration has been well studied, while the regulations of free radicals, DNA mutation and glucose metabolism are the current hot spots. This paper reviews the elaborate progress in the regulation of HIF-1 activity, which is expected to be helpful to research on anti-tumor drugs targeting HIF-1.