Hosokawa Y, Okumura K, Terashima S, Sakakura Y
Division of Medical Life Sciences, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori 0.6-8564, Japan.
Radiat Prot Dosimetry. 2012 Nov;152(1-3):159-63. doi: 10.1093/rpd/ncs215. Epub 2012 Aug 26.
We examined the effects of 5-Gy radiation on the expression of hypoxia-inducible factor-1α (HIF-1α) and the radiosensitivity of five human oral squamous cell carcinoma (OSCC) cell lines (SAS, Ca9-22, TT, BSC-OF and IS-FOM). In all of the cell lines, HIF-1α was expressed in mRNA, and radiation had no influence on gene transcription. The number of apoptotic cells increased 72 h after irradiation in cell lines SAS, Ca9-22 and TT cells, indicating low transcriptional levels of HIF-1α, and the levels of non-cleaved caspase-3, an executioner of apoptosis, and non-cleaved poly (adenosine diphosphate-ribose) polymerase (PARP), a marker of DNA damage early in apoptosis, decreased simultaneously. Conversely, radiation failed to induce apoptosis or to decrease expression of non-cleaved caspase-3 and PARP in cell lines BSC-OF and IS-FOM cells that expressed high levels of HIF-1α. BSC-OF and IS-FOM cells exhibited high migratory capacity. When CoCl(2) was present in the medium, HIF-1α expression increased along with the survival of Ca9-22 cells after radiation exposure. These results suggest that OSCC cells expressing high levels of HIF-1α are resistant to radiation. HIF-1α can be used to control the short-term radiosensitivity of cells.
我们研究了5吉电子伏特辐射对缺氧诱导因子-1α（HIF-1α）表达以及五种人类口腔鳞状细胞癌（OSCC）细胞系（SAS、Ca9-22、TT、BSC-OF和IS-FOM）放射敏感性的影响。在所有细胞系中，HIF-1α均以信使核糖核酸形式表达，且辐射对基因转录无影响。在SAS、Ca9-22和TT细胞系中，照射后72小时凋亡细胞数量增加，表明HIF-1α转录水平较低，同时凋亡执行者非切割型半胱天冬酶-3以及凋亡早期DNA损伤标志物非切割型聚（二磷酸腺苷-核糖）聚合酶（PARP）的水平同时降低。相反，在高表达HIF-1α的BSC-OF和IS-FOM细胞系中，辐射未能诱导凋亡，也未能降低非切割型半胱天冬酶-3和PARP的表达。BSC-OF和IS-FOM细胞表现出高迁移能力。当培养基中存在氯化钴时，辐射暴露后HIF-1α表达增加，同时Ca9-22细胞存活。这些结果表明，高表达HIF-1α的OSCC细胞对辐射具有抗性。HIF-1α可用于控制细胞的短期放射敏感性。
