摘要
目的观察分次电离辐射对食管癌细胞EC9706的缺氧基因HIF-1α及耐药基因MDR1表达水平的影响。方法对食管癌细胞进行1Gy·2/d分次外照射,共20次。采用实时定量PCR及Western blotting对外照射前后处于缺氧/常氧培养下的食管癌细胞EC9706的HIF-1α和MDR1表达水平进行检测。MTT及克隆形成实验被用来评估细胞的存活率及化疗耐药指数。结果单纯照射组及单纯缺氧组的HIF-1α和MDR1表达均较对照组明显升高(P<0.05),且以单纯缺氧组为著。同缺氧+照射组对比,单纯照射组细胞的存活分数显著减低(P<0.05)。单纯缺氧组的HIF-1α、MDR1表达水平显著高于缺氧+照射组(P<0.05)。结论缺氧是导致食管癌细胞化疗耐药及放射抗拒产生的较强因素。缺氧条件下分次外照射可以缓解食管癌细胞的缺氧程度,降低耐药指数,推测其后续化疗疗效应较好。
Objective To examine the effect of fractioned ionizing radiation on the expression of hypoxia inducible factor-1α （HIF-1α） and multidrug resistance （MDR1） in human esophageal cancer cells. Methods The mRNA and protein levels of HIF-1α and MDR1 in esophageal caner EC9706 cells incubated in the presence of 150 μmol/L CoCl2 were measured before and after the irradiation by quantitative RT-PCR and Western blotting, respectively. The chemosensitivity and radiosensitivity of the cells were analyzed by MTT assay and clone formation assay. Results MDR1 and HIF1α expressions were significantly up-regulated in the cells following hypoxia or irradiation （P0.05）. The surviving cell fraction in the exclusive irradiation group was significantly lower than that irradiation＋hypoxia group （P0.05）. Compared with exclusive hypoxia group, MDR1 and HIF1α expressions were decreased significantly in irradiation＋hypoxia group （P0.05）. HIF1α expression showed a positive correlation to MDR1 expression （P0.01）. Conclusion Hypoxia is an important factor to induce resistance to chemoand radiotherapy. Low-dose fractioned irradiation can lower MDR1 and HIF1α expressions in esophageal cancer cells, which should be considered when combining radiotherapy chemotherapy for esophageal cancer patients.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2010年第5期1037-1040,共4页
Journal of Southern Medical University
基金
陕西省卫生厅基金(08E06)
关键词
食管肿瘤
缺氧诱导因子
多药耐药基因
电离辐射
esophageal neoplasm
hypoxia inducible factor-1α
multidrug resistance gene
ionizing radiation
