替拉扎明調節(jié)乏氧誘導鼻咽癌細胞HIF-1α和OPN mRNAs的表達及放射增敏作用的研究
發(fā)布時間:2018-05-08 03:33
本文選題:替拉扎明 + 鼻咽癌; 參考:《廣西醫(yī)科大學》2010年碩士論文
【摘要】: 目的:研究HNE-1EB+和CNE-1EB-人鼻咽癌細胞乏氧相關基因乏氧誘導因子1α(HIF-1α)和骨橋蛋白(OPN)的差異表達以及替拉扎明(TPZ)的放射增敏作用。 方法:在常氧和乏氧條件下,用MTT法測定TPZ對HNE-1和CNE-1細胞的生長抑制作用,計算出IC50;用RT-PCR測定TPZIC10作用24小時后HNE-1和CNE-1細胞HIF-1α和OPN mRNAs的表達;以及用克隆形成法測定TPZ預作用6小時和1~6Gy 60 Coγ-射線照射后細胞的存活率,用單擊多靶數(shù)學模型擬合劑量-生存曲線,計算出D0、Dq和放射增敏比(SER)。 結果:在常氧和乏氧條件下,TPZ對HNE-1和CNE-1細胞的IC50分別為34.81μmol/L、35.02μmol/L,30.20μmol/L和28.48μmol/L;TPZ能明顯下調HNE-1細胞乏氧后HIF-1α和OPN的表達,對CNE-1HIF-1α和OPN的表達無明顯作用;放射劑量-生存曲線符合單擊多靶數(shù)學模型特征;HNE-1aero和HNE-1hypox的D0和Dq分別為0.89Gy、0.28Gy,1.47Gy和0.44Gy;HNE-1hypox/TPZ的D0和Dq分別為0.66Gy和0.21Gy;CNE-1aero和CNE-1hypox的D0和Dq分別為0.72Gy、0.68Gy,0.95Gy和0.56Gy;CNE-1hypox/TPZ的D0和Dq分別為0.85Gy和0.79Gy。 結論:TPZ對EB病毒陽性的HNE-1細胞明顯的放射增敏作用可能與其下調乏氧誘導的HIF-1α和OPN表達有關,以及具有乏氧修飾劑的作用。
[Abstract]:Aim: to study the differential expression of hypoxia inducible factor 1 偽 (HIF-1 偽) and osteopontin (OPN) in HNE-1EB and CNE-1EB- human nasopharyngeal carcinoma cells and the radiosensitization effect of telazamine. Methods: under normoxic and hypoxic conditions, the growth inhibition of TPZ on HNE-1 and CNE-1 cells was determined by MTT assay, and the expression of HIF-1 偽 and OPN mRNAs in HNE-1 and CNE-1 cells was measured by RT-PCR after 24 hours of TPZIC10 treatment. The survival rate of the cells after 6 hours of TPZ preexposure and 1~6Gy 60Co 緯 -ray irradiation was measured by clone formation method. The dose-survival curve was fitted with a single click multi-target mathematical model, and the D0 Dq and the radiosensitization ratio (SERN) were calculated. Results: under normoxic and hypoxic conditions, the IC50 of HNE-1 and CNE-1 cells were 34.81 渭 mol / L, 35.02 渭 mol / L, 30.20 渭 mol/L and 28.48 渭 mol / L, respectively, and the expression of HIF-1 偽 and OPN in HNE-1 cells after hypoxia was significantly down-regulated, but the expression of CNE-1HIF-1 偽 and OPN was not obvious. The D0 and DQ of HNE-1 aero and HNE-1hypox were 0.89 Gy 0.28 Gy and 0.44 Gy HNE-1 路TPZ D0 and DQ respectively were 0.66Gy and 0.21 Gy CNE-1aero and CNE-1hypox D0 and DQ respectively. Conclusion the apparent radiosensitization of HNE-1 cells induced by Epstein-Barr virus may be related to its down-regulation of HIF-1 偽 and OPN expression induced by hypoxia and the effect of hypoxia modifier.
【學位授予單位】:廣西醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2010
【分類號】:R739.63
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