亚硒酸钠联合阿霉素前体药通过丝裂原活化蛋白激酶信号通路介导胃癌细胞SGC-7901的增殖凋亡  

Sodium selenite combined prodrug of adriamycin mediated the proliferation and apoptosis of gastric cancer cell SGC - 7901 through mitogen - activated protein kinase signal pathwaY

作　　者：吴泉峰 方孝俊 杨小琴 陈元杏 张碧涛 张娟 孙建华 Wu Quanfeng;Fang Xiaojun;Yang Xiaoqin;Chen Yuanxing;Zhang Bitao;Zhang Juan;Sun Jianhua(Department of Gastrointestinal Surgery,the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi 445000,China（Wu QF,Yang XQ,Chen YX,Zhang BT,Sun JH;Hubei Selenium and Human Health Institute,Enshi 445000,China（Wu QF,Fang X J,Chen YX,Zhang BT,Zhang J,Sun JH;Medical School of Hubei University for Nationalities,Eushi 445000,China（Yank X)

机构地区：[1]恩施州中心医院胃肠外科,445000 [2]湖北硒与人体健康研究所 [3]湖北民族学院医学院,恩施445000

出　　处：《中华实验外科杂志》2018年第10期1874-1877,共4页Chinese Journal of Experimental Surgery

基　　金：湖北省自然科学基金（2016CFB668）;恩施州中心医院“硒与人体健康”科研项目;国家自然科学基金（81770283）;武汉市腹膜癌临床医学研究中心资助项目（2015060911020462）

摘　　要：目的探讨亚硒酸钠联合阿霉素前体药（PADM）对胃癌细胞SGC-790l增殖、凋亡的影响及其机制。方法以2．93μg／ml亚硒酸钠和2μg／mlPADM处理胃癌SGC-7901细胞48h后采用噻唑蓝（MTT）法检测各组SGC-7901细胞的增殖能力。采用流式细胞仪检测各组SGC-7901细胞的凋亡水平。反转录．聚合酶链反应（RT．PCR）和Westernblot检测各组SGC-7901细胞丝裂原活化蛋白激酶（MAPK）信号通路相关因子[细胞外信号调节激酶1／2（ERK1／2）、p38、c-Jun氨基末端激酶（JNK）]的表达和蛋白活化。结果与对照组（不加药的SGC-7901细胞）（0．873±0．055）比较，砸硒酸钠组（0．551±0．032）和PADM组（0．610±0．023）均能明显地降低胃癌细胞SGC-7901的增殖能力（P=0．001、0．001）；与单药组比较，药物联用后（0．234±0．022）抑制效果更明显（P=0．000、0．000）。与对照组（11．4134-1．676）比较，亚硒酸钠组（23．530±0．943）和PADM组（23．207±2．294）均能明显促进胃癌细胞SGC-7901的凋亡（P=0．000、0．001）；与单药组比较，两种药物联用后（54．827±4．048）作用促凋亡效果更显著（P=0．000、0．000）。亚硒酸钠和PADM能明显地下调ERKl／2的mRNA表达和蛋白活性，上调p38和JNK的mRNA表达和蛋白活性，且两种药物联用后作用效果更显著。结论亚硒酸钠联合PADM可明显抑制胃癌细胞SGC-7901的增殖，促进SGC-7901细胞凋亡且效果强于单用药物，其作用机制可能与抑制ERKl／2活化，增强p38MAPK和JNK活化有关。Objective To investigate the effects of sodium selenite combined with prodrug of adri- amycin （PADM） on the proliferation and apoptosis of gastric cancer cell SGC -7901. Methods According to half maximal inhibitory concentration （ICs0） from the pre -experiment, the SGC -7901 ceils were treated with 2. 93 μg/rnl sodium selenite and 2 μg/ml PADM. After treatment with 48 h, methyl thiazol tetrazolium （MTT） assay was used to detect the proliferation of SGC-7901 cells. The apoptosis of SGC-7901 cells was detected by flow cytometry. The expression of mitogenactivated protein kinase （MAPK） signal related mRNAs were measured using reverse transcriptase - polymerase chain reaction（ RT - PCR） and the activation of MAPK signal was detected using Western blotting. Results Compared with control （0. 873 ± 0. 055 ） , Sodium selenite （0. 551 ± 0. 032） and PADM （0. 610 ± 0. 023 ） can signif- icantly reduce the proliferation of gastric cancer SGC - 7901 cells （ P = 0. 001, 0. 001 ）. The proliferation of SGC-7901 cells was inhibited in Sodium selenite combined with PADM （0. 234 ± 0. 022） compared with single （ P = 0. 000, 0. 000）. Compared with control （ 11. 413 ± 1. 676 ）, Sodium selenite （23. 530 ± 0. 943） and PADM （23. 207 ± 2. 294） can markedly promote the apoptosis of SGC - 7901 cells （ P = 0. 000, 0. 001 ）. The apoptosis of SGC -7901 cells was increased in Sodium selenite combined with PADM （54. 827 ± 4. 048） compared with single （ P = 0. 000, 0. 000）. Sodium selenite and PADM significantly decreased the mRNA expression and activation of extracellular signal -regulated kinase 1/2 （ERK1/2）, upregulated mRNA expression and activation of p38MAPK and c -Jun N -terminal kinase （JNK）. The effect was more pronounced after the combination of the two drugs. Conclusion Sodium selenite joint PADM can obviously inhibit proliferation of gastric cancer SGC -7901 cells, promote apoptosis of the SGC-7901 cell. Its mechanism may be related to inhibition of E

关 键 词：亚硒酸钠 阿霉素前体药 胃癌细胞SGC-7901 丝裂原活化蛋白激酶信号通路 

分 类 号：R364.4[医药卫生—病理学]