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Expression of hypoxia-inducible factor-1alpha (HIF-lalpha) and correlation with radiation resistance in human oral squamous cell carcinoma cell lines.

人口腔鳞状细胞癌细胞系缺氧诱导因子-1α（HIF-1α）的表达及其与放射抵抗的相关性。

基本信息

批准号：
15592001
负责人：
HOSOKAWA Yoichiro
金额：
$ 2.18万
依托单位：
Health Scienses University of Hokkaido
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The relationship between hypoxia-inducible factor (HIF)-1alpha and radiation resistance in tumor cells has been unknown. We examined the effects of 5 Gy radiation under normoxia on the expression of HIF-1alpha, apoptosis, and migration capacity of five human oral squamous cell carcinoma (OSCC) lines. Cells in all of the lines expressed HIF-1alpha mRNA, and radiation had no influence on gene transcription. Western blot analysis did not detect the p53 tumor suppressor, which induces apoptosis through HIF-1alpha degradation, either before or after radiation exposure. Numbers of apoptotic cells increased 72 h after irradiation in lines TT, Ca9-22, and SAS, indicating low transcriptional levels of HIF- lalpha, and levels of non-cleaved caspase-3, an executioner of apoptosis, and non-cleaved poly (ADP-ribose) polymerase (PARP), a marker of DNA damage early in apoptosis, decreased at the same time. On the other hand, radiation failed to induce apoptosis or to decrease levels of non-cleaved caspase-3 and PARP in lines IS-FOM and BSC-OF, which express HIF-1alpha at high levels. Cell lines IS-FOM and BSC-OF showed high migration capacity. The other cell lines showed low capacity. These results suggest that OSCC cells expressing a high level of HIF-1alpha are resistant to radiation.

低氧诱导因子（HIF）-1 α与肿瘤细胞辐射抗性的关系尚不清楚。我们研究了在常氧条件下5戈伊照射对5个人口腔鳞状细胞癌（OSCC）细胞系HIF-1 α表达、细胞凋亡和迁移能力的影响。所有细胞系均表达HIF-1 α mRNA，辐射对基因转录无影响。Western印迹分析没有检测到p53肿瘤抑制因子，其通过HIF-1 α降解诱导细胞凋亡，无论是在辐射暴露之前还是之后。在TT、Ca 9 -22和SAS系中，照射后72 h凋亡细胞的数量增加，表明HIF-1 α的转录水平较低，同时凋亡的执行者非切割的caspase-3和凋亡早期DNA损伤的标记物非切割的聚（ADP-核糖）聚合酶（PARP）的水平降低。另一方面，辐射不能诱导细胞凋亡或降低细胞系IS-FOM和BSC-OF中未切割的caspase-3和PARP的水平，它们以高水平表达HIF-1 α。细胞系IS-FOM和BSC-OF显示出高迁移能力。其他细胞系显示低容量。这些结果表明，表达高水平HIF-1 α的OSCC细胞对辐射具有抗性。