Luo Dongjun, Wang Zhongxia, Wu Junyi, Jiang Chunping, Wu Junhua
Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
Biomed Res Int. 2014;2014:409272. doi: 10.1155/2014/409272. Epub 2014 Jul 2.
Hypoxia is a common feature of many solid tumors, including hepatocellular carcinoma (HCC). Hypoxia can promote tumor progression and induce radiation and chemotherapy resistance. As one of the major mediators of hypoxic response, hypoxia inducible factor-1 (HIF-1) has been shown to activate hypoxia-responsive genes, which are involved in multiple aspects of tumorigenesis and cancer progression, including proliferation, metabolism, angiogenesis, invasion, metastasis and therapy resistance. It has been demonstrated that a high level of HIF-1 in the HCC microenvironment leads to enhanced proliferation and survival of HCC cells. Accordingly, overexpression, of HIF-1 is associated with poor prognosis in HCC. In this review, we described the mechanism by which HIF-1 is regulated and how HIF-1 mediates the biological effects of hypoxia in tissues. We also summarized the latest findings concerning the role of HIF-1 in the development of HCC, which could shed light on new therapeutic approaches for the treatment of HCC.
缺氧是包括肝细胞癌(HCC)在内的许多实体瘤的常见特征。缺氧可促进肿瘤进展并诱导放疗和化疗耐药。作为缺氧反应的主要介质之一,缺氧诱导因子-1(HIF-1)已被证明可激活缺氧反应基因,这些基因参与肿瘤发生和癌症进展的多个方面,包括增殖、代谢、血管生成、侵袭、转移和治疗耐药。已经证明,HCC微环境中高水平的HIF-1会导致HCC细胞增殖和存活增强。因此,HIF-1的过表达与HCC的不良预后相关。在这篇综述中,我们描述了HIF-1的调控机制以及HIF-1如何介导组织中缺氧的生物学效应。我们还总结了关于HIF-1在HCC发生发展中作用的最新发现,这可能为HCC的治疗提供新的治疗方法。