腺病毒介导的ING4联合化疗药物增强对胃癌细胞SGC-7901增殖的抑制作用  

Enhanced inhibitory effect of adenovirus-mediated ING4 combined with chemotherapy agent on growth of gastric carcinoma cell line SGC-7901

作　　者：陆向东[1] 谭洁[1] 杨吉成[2] 程晓赪 周俊东[1] 李汉冲[1] 

机构地区：[1]南京医科大学附属苏州医院血液肿瘤科,江苏苏州215001 [2]苏州大学细胞与分子生物学教研室,江苏苏州215123

出　　处：《现代肿瘤医学》2009年第5期805-808,共4页Journal of Modern Oncology

基　　金：江苏省苏州市自然科学基金项目(编号:SZD0784);南京医科大学自然科学基金项目(编号:NY07013)

摘　　要：目的:探讨腺病毒介导的ING4基因(Ad-ING4)与化疗药物联合应用增强对胃癌细胞株SGC-7901增殖的抑制效果。方法:用Ad-ING4感染胃癌细胞株SGC-7901,RT-PCR法检测ING4基因在胃癌细胞中的转录,用Ad-ING4分别联合化疗药物氟尿嘧啶(fluorouracil5-FU)和顺铂(cisplatin DDP)处理培养的胃癌细胞株SGC-7901,MTT法检测细胞增殖抑制率,流式细胞术(FCM)检测细胞周期和凋亡率。结果:Ad-ING4感染SGC-7901细胞后,RT-PCR结果提示有目的基因的转录。MTT结果显示,100MOIAd-ING4与25μg/ml5-FU联合应用后120小时,SGC-7901细胞增殖抑制率达(94±0.50)%,显著高于单用Ad-ING4组的(65.05±2.03)%和5-FU组的(62.54±0.73)%(均P<0.05);100MOIAd-ING4与6.25μg/mlDDP联合应用后120小时,SGC-7901细胞增殖抑制率达(97.54±0.54)%,显著高于单用Ad-ING4组的(65.05±2.03)%和DDP组的(55.14±1.21)%(均P<0.05)。流式细胞术检测结果显示,Ad-ING4与5-FU或DDP联合应用明显导致细胞S期减少、G2/M期阻滞;Ad-ING4联合5-FU组细胞凋亡率为(16.2±1.18)%,显著高于单用Ad-ING4组的(8.17±0.85)%和5-FU组的(7.4±0.89)%(均P<0.05);Ad-ING4联合DDP组细胞凋亡率为(14.17±1.77)%,显著高于单用Ad-ING4组的(8.17±0.85)%和DDP组的(5.93±0.87)%(均P<0.05)。结论:Ad-ING4与5-FU或DDP联合应用能显著提高对胃癌细胞株SGC-7901增殖的抑制作用。Objective： To investigate the inhibitory effect of adenovirus - mediated INC.4 （ Ad - ING4 ） combined with fluorouracil（5 - FU） or cisplatin（DDP） on growth of human gastric carcinoma cell line SGC -7901. Methods： The ING4 gene was transfected into human gastric carcinoma cell line SGC - 7901 with a replication - incompetent adenovirus vector. The mRNA transcriptions of ING4 in SGC -7901 cells was confirmed using RT -PCR;Humau gastric carcinoma cell line SGC -7901 was treated with Ad -ING4 combined with 5 -FU or DDP separately. The growth inhibition rate of cells was analyzed by MTF assay;The cell cycle and apoptosis were detected by flow cytometry （FCM）. Results：ING4 was proved successful transcription in SGC -7901 cells. Five days after combined treatment with Ad - ING4（ 100 MOI） and 5 - FU（25μg/ml） ,the growth inhibitory rate of SGC -7901 cells was （94 ±0.5） %, which was significantly higher than those in Ad - INC-4 group [ （ 65.05 ± 2.03 ） % , P 〈 0.05 ] and 5 - FU group [ （ 62.54 ± 0.73 ） % , P 〈 0. 051 ; five days after combined treatment with Ad - ING4 （ 100 MOI） and DDP （ 6.25 μg / ml） ,the growth inhibitory rate was（97.54±0.54）% ,which was also significantly higher than those in Ad -ING4 group[ （65.05 ±2.03）% ,P 〈0.05 ] and DDP group[ （55.14± 1.21 ）% ,P 〈0.05]. FCM showed that combined administration of Ad - ING4 and 5 - FU or DDP remarkably reduced S phase and arrested SGC - 7901 cells at G2/M phase. The cell apoptotic rate was （ 16.2± 1. 18） % in Ad - ING4 and 5 - FU group, which was significantly higher than those in Ad - ING4 group [ （ 8.17 ± 0. 85 ） %, P 〈 0. 05 ], and 5 - FU group [ （ 7.4 ± 0.89 ） %, P 〈 0.05 ]. The cell apoptotic rate was （14.17± 1.77 ）% in Ad -INCA and DDP group,which was significantly higher than those in Ad - ING4 group [ （ 8.17 ±0.85 ） %, P 〈 0. 05 ] and DDP group [ （ 5.93 ± 0.87 ） %, P 〈 0.05 ]. Conclusion： Ad - ING4 combined with 5 - FU or DDP has enhanced inh

关 键 词：ING4 胃癌 基因治疗 化学疗法 氟尿嘧啶 顺铂 

分 类 号：R73-362[医药卫生—肿瘤]