论文部分内容阅读
在实体瘤中,无论是良性肿瘤,还是恶性肿瘤,低氧都是一种普遍现象,并且绝大多数肿瘤中存在低氧微环境。低氧与肿瘤的恶性进展、放射与化疗的耐受性和不良的预后有着密切的联系。缺氧诱导因子1(hypoxia inducible factor-1,HIF-1)广泛存在于大多数肿瘤组织中,并且HIF-1是一种存在于低氧条件下的转录因子。它是由氧调控表达的HIF-1α亚基与组成型表达的HIF-1β亚基组成的异二聚体。在常氧环境下,通过激活泛素蛋白酶体及氧依赖性降解区域的脯氨酸羟化而使HIF-1α迅速降解,半衰期约为5 min,而在低氧状态下,HIF-1α与β亚基二聚化并稳定存在。二聚化的HIF-1能够促进癌细胞的增殖、迁移以及侵袭。因此,HIF-1α有可能成为抑制癌细胞生长迁移与侵袭的靶点,这将为化疗及高压氧治疗提供新的思路。综述近年国内外抗氧化环境下HIF-1基因所主导的与癌细胞迁移和侵袭及其抑制相关的分子机理的研究,以便通过在抗炎、抗氧化条件下的增氧作用机理改进化疗效果。
In solid tumors, whether it is benign or malignant tumors, hypoxia is a common phenomenon, and the vast majority of tumors exist hypoxic microenvironment. Hypoxia and malignant tumor progression, radiation and chemotherapy tolerance and poor prognosis are closely linked. Hypoxia inducible factor-1 (HIF-1) is widely found in most tumor tissues and HIF-1 is a transcription factor that exists under hypoxic conditions. It is a heterodimer consisting of a hypoxia-regulated HIF-1 alpha subunit and a constitutively expressed HIF-1 beta subunit. Under normoxic conditions, HIF-1α is rapidly degraded by activating proline hydroxylation in ubiquitin proteosomes and oxygen-dependent degradation regions with a half-life of approximately 5 min, whereas in hypoxia HIF-1α and β Subunits dimerize and are stable. Dimerized HIF-1 promotes proliferation, migration and invasion of cancer cells. Therefore, HIF-1α may become a target for inhibiting the growth, migration and invasion of cancer cells, which will provide a new idea for chemotherapy and hyperbaric oxygen therapy. This review summarizes the molecular mechanisms underlying HIF-1-induced cancer cell migration and invasion and its inhibition in recent years in order to improve the chemotherapeutic effect through the mechanism of oxygenation under anti-inflammatory and anti-oxidative conditions.