Cancer Research Center, Shandong Tumor Hospital, Jinan, Shandong Province, PR China.
J Cell Biochem. 2010 Oct 15;111(3):554-63. doi: 10.1002/jcb.22739.
Hypoxia plays an important role in the development of solid tumors and is associated with their therapeutic resistance. There exist three major forms of hypoxia: acute, chronic, and intermittent hypoxia. Previous studies have shown that cancer cells could behave in the form of adaptation to hypoxia in tumor growth, which could result in their biological changes and determine their responses to the therapies. To investigate the tumor cells' adaptation to hypoxia, we recreated two models using two lung cancer cell lines in the presence of intermittent hypoxia, which is characterized by changes in oxygen pressure within the disorganized vascular network. We investigated biological behaviors such as cell cycle, proliferation, radiation sensitivity, apoptosis and migration, hypoxia signal pathway in the lung cancer cells treated with chronic intermittent hypoxia, as well as the role of hypoxia inducible factor 1 there, hypoxia-inducible genes analyzed by real-time RT-PCR chip in H446 cells treated with the model. The results indicated the changes of some hypoxia target gene expressions of those induced by hypoxia, some of which were confirmed by real-time RT-PCR. The cells mediated by irradiation induced resistance to radiation and apoptosis and increased metastasis in lung cancer cells. It was found that such changes were related to hypoxia inducible factor 1, alpha subunit (HIF-1α).
缺氧在实体肿瘤的发展中起着重要作用，并与肿瘤的治疗抵抗有关。存在三种主要形式的缺氧：急性、慢性和间歇性缺氧。先前的研究表明，肿瘤生长过程中，癌细胞可以通过适应缺氧来表现，这可能导致其生物学变化，并决定其对治疗的反应。为了研究肿瘤细胞对缺氧的适应，我们使用两种肺癌细胞系在间歇性缺氧的存在下创建了两种模型，间歇性缺氧的特点是紊乱的血管网络中的氧压变化。我们研究了生物学行为，如细胞周期、增殖、辐射敏感性、凋亡和迁移，慢性间歇性缺氧处理后的肺癌细胞中的缺氧信号通路，以及缺氧诱导因子 1 在其中的作用，通过实时 RT-PCR 芯片分析 H446 细胞中模型处理后的缺氧诱导基因。结果表明，一些缺氧诱导的靶基因表达发生了变化，其中一些通过实时 RT-PCR 得到了证实。辐射诱导的细胞对辐射的耐药性、凋亡和肺癌细胞转移增加。研究发现，这些变化与缺氧诱导因子 1，α亚基（HIF-1α）有关。
