光辉霉素对胃癌细胞周期、凋亡的影响及可能机制  

Effect of mithramycin on cell cycle and apoptosis of gastric cancer cells and its possible mechanism

作　　者：何灏澜[1] 李倩 姜晗[1] 王晓[1] 陆明[1] HE Haolan;LI Qian;JIANG Han;WANG Xiao;LU Ming(Department of Gastroenterology,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024,China)

机构地区：[1]沈阳医学院附属中心医院消化内科,沈阳110024

出　　处：《临床肿瘤学杂志》2019年第2期133-136,共4页Chinese Clinical Oncology

摘　　要：目的探讨光辉霉素(MTM)对胃癌细胞周期、凋亡的影响及可能的机制。方法体外培养胃癌BGC-823、SGC-7901、MKN-28、AGS和正常胃黏膜GES-1细胞,采用实时荧光定量(QPCR)和Western blotting检测SP1 mRNA和蛋白表达。0、25、50、100 nmol/L MTM处理BGC-823细胞24 h,QPCR和Western blotting检测SP1、p53、p21 mRNA和蛋白表达。流式细胞术检测50 nmol/L MTM处理BGC-823细胞周期和凋亡的变化。结果 QPCR检测胃癌BGC-823、SGC-7901、MKN-28、AGS细胞系中SP1 mRNA表达量为6. 12±0. 15,5. 42±0. 24,3. 33±0. 21,3. 01±0. 12,均显著高于GES-1细胞(P<0. 05); Western blotting检测SP1蛋白表达与mRNA表达一致。0、25、50、100 nmol/L MTM处理BGC-823细胞,SP1 mRNA和蛋白表达逐渐降低,p53、p21 mRNA和蛋白表达逐渐升高。50 nmol/L MTM组SP1表达量最低(mRNA:0. 48±0. 12;蛋白:0. 28±0. 09),p53表达量最高(mRNA:5. 37±0. 45;蛋白:1. 29±0. 20); 100 nmol/L MTM组p21表达量最高(mRNA:4. 92±0. 53;蛋白:0. 86±0. 15);与0 nmol/L MTM组比较,差异具有统计学意义(P<0. 05)。流式细胞术结果显示,50 nmol/L MTM组BGC-823细胞G0/G1比例为(63. 71±2. 14)%和凋亡率为(24. 68±1. 09)%,均明显高于0 nmol/L MTM组[(57. 39±1. 83)%和(9. 23±0. 75)%],差异具有统计学意义(P<0. 05)。结论 MTM通过降低SP1、上调p53、p21表达水平来增加胃癌细胞周期阻滞,诱导凋亡。Objective To investigate the effect of mithramycin(MTM)on cell cycle and apoptosis of gastric cancer cells and its possible mechanism.Methods BGC-823,SGC-7901,MKN-28,AGS and normal gastric mucosa GES-1 cells were cultured in vitro.Real-time fluorescence quantitative analysis(QPCR)and Western blotting were used to detect the expression of SP1 mRNA and protein.BGC-823 cells were treated with 0,25,50 and 100 nmol/L MTM for 24 hours.The expression of SP1,p53 and p21 were detected by QPCR and Western blotting.Flow cytometry was used to detect the changes of cell cycle and apoptosis in BGC-823 cells treated with 50 nmol/L MTM.Results The expression of SP1 in BGC-823,SGC-7901,MKN-28 and AGS cell lines was 6.12±0.15,5.42±0.24,3.33±0.21 and 3.01±0.12 by QPCR,which were significantly higher than those in GES-1 cell lines(P<0.05).Western blotting showed that the expression of SP1 protein was consistent with that of mRNA.When BGC-823 cells were treated with 0,25,50 and 100 nmol/L MTM,the expression of SP1 decreased gradually,while the expression of p53 and p21 increased gradually.Compared with 0 nmol/L MTM group,the expression of SP1 was the lowest and p53 was the highest in 50 nmol/L MTM group and the expression of p21 was the highest in 100 nmol/L MTM group(P<0.05).Flow cytometry showed that the G 0/G 1 ratio and apoptotic rate of BGC-823 cells in 50 nmol/L MTM group were(63.71±2.14)%and(24.68±1.09)%respectively,which were significantly higher than those in 0 nmol/L MTM group.Conclusion Mithramycin can increase cell cycle arrest and induce apoptosis by decreasing SP1,increasing p53 and p21 expression.

关 键 词：胃癌 SP1 光辉霉素 P53 P21 

分 类 号：R735.2[医药卫生—肿瘤]