PD98059和LY294002对乏氧放射胰腺癌ASPC-1细胞的影响  

Effect of PD98059 and LY294002 on ASPC-1 cell line accepted hypoxia and radiation

作　　者：李建军[1] 李光[1] 刘意[1] 陈延治[1] 王志宇[1] 辛彦[2] 

机构地区：[1]中国医科大学附属第一医院放疗科,辽宁沈阳110001 [2]中国医科大学附属第一医院肿瘤研究所第四研究室,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2007年第4期269-272,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:观察MAPK、PI3K信号传导通路抑制剂PD98059(PD)、LY294002(LY)对乏氧照射胰腺癌细胞系ASPC-1细胞周期、VEGF和EGFR蛋白表达及细胞存活的影响。方法:AS-PC-1细胞分成常氧组、乏氧组、PD乏氧组、LY乏氧组和PD+LY乏氧组及各自照射组;PD98059终浓度为25μmol/L,LY294002终浓度为20μmol/L。乏氧组乏氧时间为24h,照射组接受4Gy单次照射,乏氧照射组在乏氧情况下进行照射。用Westernblot法、流式细胞术以及成克隆分析法对ASPC-1细胞进行检测。结果:常氧情况下ASPC-1细胞VEGF、EGFR蛋白均有表达,ASPC-1细胞乏氧培养后VEGF、EGFR蛋白表达量增加,应用PD98059或(和)LY294002后乏氧VEGF、EGFR蛋白的表达量较单纯乏氧组降低,LY乏氧组或PD+LY乏氧组VEGF表达蛋白量较PD乏氧组减少。乏氧组细胞克隆形成率较常氧组降低,LY乏氧组细胞克隆形成率较PD乏氧组降低,但差异无统计学意义,F=3·51,P=0·053。照射组间细胞克隆形成率差异均有统计学意义,F=123·21,P=0·0005,LY乏氧照射组细胞克隆形成率低于PD乏氧照射组,PD+LY乏氧照射组的细胞克隆形成率低于单独应用组。结论:MAPK、PI3K传导通路抑制剂PD98059、LY294002可降低乏氧后ASPC-1细胞VEGF、EGFR蛋白表达及乏氧照射后细胞克隆形成率,ASPC-1细胞乏氧后PI3K传导通路的激活可能起主要作用。OBJECTIVE： To investigate the effect of PD98059 （PD） and LY294002 （LY）, inhibitors of phosphatidylinositol 3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways, on the cell cycles, VEGF and EGFR protein expressions, and the cell survival of the human pancreas cancer cell line （ASPC-1） under hypoxia conditions accepted radiation or not. METHODS： ASPC-1 cells were assigned to normal oxygen group, hypoxia group, PD hypoxia group, LY hypoxia group, PD＋LY hypoxia group and their radiation groups respectively. PD98059 final concentration was 25 μmol/L and LY294002 was 20 μmol/L. Hypoxic groups were exposured in hypoxia condition for 24 h. Radiation groups and hypoxia radiation group were treated with the dose of 4 Gy X-ray. ASPC-1 cells, which were treated with LY294002 or/and PD98059 before hypoxia, were measured by flow cytometry, Western blot and the cologenic survival assay. The plating efficiency of the cells irradiated or not were assessed by the cologenic survival assay after the 14-day culture. RESULTS： The results showed ASPC-1 cells expressed VEGF and EGFR proteins under normal oxygen condition. After exposured in LY294002 and/or LY294002, the expressions of VEGF and EGFR proteins remarkably decreased under hypoxia conditions in ASPC-1 cells. There was no significantly differentia between plating efficiencys of hypoxia groups and normal oxygen group cells without accepted 4 Gy radiation, F= 3.51, P=0. 053. But there was significantly differentia between plating efficiencys of cells accepted 4 Gy radiation, F=123.21, P=0. 000 5. The plating efficiency of hypoxia radiation group were higher than that of normal oxygen radiation group. Hypoxic ASPC-1 cells accepted irradiation treated with LY294002 had lower plating efficiency than that with PD98059. The plating efficiency of ASPC-1 cell under the cooperation of LY294002 and PD98059 had a remarkably descrease than that under either one alone. CONCLUSIONS： Treatment with either LY or PD might remarkedly decrease th

关 键 词：胰腺肿瘤/放射疗法 胰腺肿瘤/代谢 蛋白激酶类/药物作用 信号传导/药物作用 细胞低氧 肿瘤细胞 培养的 

分 类 号：R735.9[医药卫生—肿瘤]