文章：

缺氧-肿瘤生长的关键调节因素

Hypoxia — a key regulatory factor in tumour growth

原文发布日期：2002-01-01

DOI: 10.1038/nrc704

类型: Review Article

开放获取: 否

要点：

1. Hypoxia is a reduction in the normal level of tissue oxygen tension, and occurs during acute and chronic vascular disease, pulmonary disease and cancer. It induces a transcription programme that promotes an aggressive tumour phenotype.
2. Hypoxia is associated with resistance to radiation therapy and chemotherapy, but is also associated with poor outcome regardless of treatment modality, indicating that it might be an important therapeutic target.
3. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor that is induced by hypoxia and regulated by a proline hydroxylase.
4. Pathways that are regulated by hypoxia include angiogenesis, glycolysis, growth-factor signalling, immortalization, genetic instability, tissue invasion and metastasis, apoptosis and pH regulation.
5. Most of the hypoxia-induced pathways promote tumour growth, but apoptosis is also induced by hypoxia. The balance of these pathways might be critical for the effects of hypoxia on tumour growth.
6. Drugs that inhibit HIF-1α expression antagonize HIF-1α interaction with CBP/p300 or block downstream function of genes such as vascular endothelial growth factor and cyclooxygenase-2 have potentially important roles in tumour therapy. Hypoxia can also be used to activate therapeutic gene delivery to specific areas of tissue.

要点翻译：

1. 缺氧是指组织氧张力正常水平的降低，发生于急慢性血管疾病、肺部疾病及癌症过程中。它会诱导一种转录程序，促进侵袭性肿瘤表型的形成。
2. 缺氧与放疗和化疗耐药性相关，但无论采用何种治疗方式，缺氧都与不良预后有关，这表明它可能是一个重要的治疗靶点。
3. 缺氧诱导因子-1α（HIF-1α）是一种关键转录因子，在缺氧条件下被诱导产生，并受到脯氨酸羟化酶的调控。
4. 缺氧调控的通路包括血管生成、糖酵解、生长因子信号传导、永生化、遗传不稳定性、组织侵袭与转移、细胞凋亡以及pH调节。
5. 大多数缺氧诱导通路会促进肿瘤生长，但缺氧也会诱导细胞凋亡。这些通路之间的平衡可能对缺氧影响肿瘤生长的效果至关重要。
6. 抑制HIF-1α表达的药物、拮抗HIF-1α与CBP/p300相互作用的药物，或阻断血管内皮生长因子和环氧化酶-2等基因下游功能的药物，在肿瘤治疗中可能具有重要作用。缺氧还可用于激活治疗性基因递送至特定组织区域。

英文摘要：

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting.

摘要翻译： 

细胞在低氧条件下会发生多种生物学反应，包括激活调控增殖、血管生成和死亡的信号通路。癌细胞已适应这些通路，使肿瘤在低氧条件下仍能存活甚至生长，而肿瘤低氧与不良预后和放疗抵抗相关。因此，低氧反应通路中的许多成分都是理想的治疗靶点。

原文链接：

Hypoxia — a key regulatory factor in tumour growth