肝缺氧诱导因子-1α与肝癌发生、发展及治疗研究新进展

Advances in understanding the relationship between hepatic hypoxia-inducible factor-1 alpha and hepatocellular carcinoma

失控的增殖导致缺氧(hypoxia)是肝细胞癌(HCC)形成的特征性微环境.缺氧可促进癌细胞增殖、转移、血管新生、抑制癌细胞分化、凋亡以及对放化疗耐受.缺氧诱导因子-1α(HIF-1α)是介导生理性和病理性低氧反应的关键转录因子,在转录水平上调控百余种靶基因,参与调节血管新生及糖代谢等过程,与HCC生长、浸润、转移和预后等密切相关.近年来以HIF-1α为靶点的基因疗法如RNA干扰、反义技术和自杀基因技术等,成为HCC辅助治疗的新策略.本文综述了HIF-1α转录水平异常与HCC发生、发展及靶向HIF-1α基因治疗HCC的新进展.

Hepatocellular carcinoma （HCC） is characterized by hypoxia due to robust cell proliferation. Hypoxia can promote tumor cell proliferation, metastasis and neovasculogenesis, inhibit differentiation and apoptosis, and decrease chemosensitivity and radiosensitivity. Hypoxia- inducible factor-1α （HIF-1α） is a key mediator of physiological and pathological hypoxia response and controls the transcription of numerous genes that are of pivotal importance for angiogenesis and cellular metabolism. Therefore, HIF-1α is closely related with the proliferation, metastasis and apoptosis of HCC cells. Recently, HIF- 1α-based gene therapy has become a novel adjunctive strategy for the management of HCC. This review focuses on the relationship between HIF-1α and the progression and therapy of HCC.