亚硒酸钠联合gossypol促进结直肠癌SW480细胞凋亡  

Selenite combined with gossypol increase apoptosis in SW480 colorectal cancer cells

作　　者：黄方[1] 黄艾[1] 马虹[1] 张秋月[1] 张涛[1] 

机构地区：[1]华中科技大学同济医学院协和医院肿瘤中心,湖北武汉430022

出　　处：《基础医学与临床》2013年第10期1309-1313,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81101507;81101573)

摘　　要：目的研究亚硒酸钠和BCL-2/BCL-xl抑制剂gossypol在诱导结直肠癌细胞凋亡中的协同作用。方法将SW480分为6μmol/L gossypol组,10μmol/L亚硒酸钠组,gossypol与亚硒酸钠联合组(6μmol/L gossypol+10μmol/L亚硒酸钠),用Western blot检测经亚硒酸钠诱导后,SW480细胞中BCL-2家族蛋白的变化;用DAPI染色法,荧光显微镜检测细胞凋亡。用不同浓度的gossypol与亚硒酸钠混合处理BAX/BAK缺乏的MEF细胞,用锥虫蓝染色检测死亡率。结果亚硒酸钠作用于细胞后,Bim和BAX蛋白水平升高,而Mcl-1和BCL-xl表达下降(P<0.05)。亚硒酸钠和gossypol联合作用后,细胞的核裂解率,死亡率均比单独作用组明显上升(P<0.05)。在BAX/BAK双缺失的细胞中,gossypol仍能发挥促凋亡的作用。结论亚硒酸钠通过Bim和BAX增加结直肠癌SW480细胞的凋亡敏感性,gossypol通过降低肿瘤细胞对细胞凋亡的抵抗性,两者产生协同作用促进结直肠癌SW480细胞凋亡。Objective We studied the potential synergistic efficacy of selenite and gossypol to induce apoptosis in SW480 colorectal cancer cells. Methods SW480 cells were divided into three groups： 6μmol/L gossypol, 10 μmol/L selenite and both of them, then we observed the apoptosis by DAPI staining and fluorescence microsco- py. Finally, we detected the cell death induced by different concentration gossypol and selenite in BAX/BAK defi- cient MEF cell. Results The expression of Bim and BAX proteins increased while Mcl-1 and BCL-xl decreased in SW480 cells after selenite administration. Nucleus fragmentation rates and cell death in SW480 were significantly increased after the combined treatment of selenite and gossypol（P 〈 0.05 ）. In BAX/BAK deficient cells, gossypol can still promote apoptosis. Conclusions Selenite and gossypol can promote apoptosis via different pathways, sele- nite increases the sensitivity of tumor cells to apoptosis through Bim and BAX, while gossypol reduced the resist- ance to apoptosis of tumor cell, and the combination of them produced synergistic effect inducing apoptosis in SW480 ceils.

关 键 词：亚硒酸钠 GOSSYPOL 凋亡 联合化疗 

分 类 号：R735.3[医药卫生—肿瘤]