HSP90抑制剂IPI-504影响胃癌细胞及其干细胞样细胞功能的研究  

Study on the effect of HSP90 inhibitor IPI-504 on gastric cancer cells and its stem cell like cells

作　　者：黄磊[1] 黄侠[2] 蔡一亭[2] 陈大伟[2] 费哲为[1] 

机构地区：[1]上海交通大学医学院附属新华医院,上海200092 [2]上海交通大学医学院附属新华医院崇明分院,上海202150

出　　处：《现代中西医结合杂志》2015年第30期3317-3320,共4页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：上海市卫生局课题(ZK2012B15)

摘　　要：目的探讨特异性热休克蛋白90(HSP90)抑制剂盐酸瑞他霉素(IPI-504)对人胃癌细胞SGC-7901、NCI-N87及其CD44+干细胞样细胞的增殖、迁移、侵袭及凋亡的影响。方法应用流式细胞仪检测及分选SGC-7901、NCI-N87中干细胞样细胞;应用MTT比色法检测不同浓度IPI-504对SGC-7901、NCI-N87及其CD44+干细胞样细胞的生长抑制率;应用平板克隆形成实验检测不同浓度IPI-504对SGC-7901、NCI-N87及其CD44+干细胞样细胞的克隆形成能力;应用划痕实验及Transwell侵袭实验检测IPI-504对SGC-7901、NCI-N87及其CD44+干细胞样细胞迁移及侵袭力;应用流式细胞仪检测IPI-504对SGC-7901、NCI-N87及其CD44+干细胞样细胞凋亡率的影响。结果从SGC-7901、NCIN87分选出8%和6%的CD44+干细胞样细胞,纯度>95%;IPI-504能显著抑制SGC-7901、NCI-N87及其CD44+干细胞样细胞增殖、克隆形成、迁移及侵袭能力,增加以上细胞的凋亡率,且呈剂量依赖性。结论 HSP90抑制剂IPI-504能够显著抑制胃癌细胞SGC-7901、NCI-N87及其CD44+干细胞样细胞的功能,并促使其凋亡。Objective It is to investigate the influence of the heat shock protein 90 （ HSP90 ） inhibitor Retaspimycin Hydrochloride （IPI-504） on the ability of proliferation, migration, invasion and apoptosis in gastric cancer cells of SGC-7901, NCI-N87 and their CD44^＋stem cell like gastric cancer cells.Methods Flow cytometry was used to detect and sort the stem cell like cells in SGC-7901, NCI-N87 gastric cancer cells.MTT colorimetric assay was utilized to compare the effort of IPI-504 on the inhibition ratio in SGC-7901, NCI-N87 and their CD44^＋stem cell like gastric cancer cells.Colony formation assay was executed to test the effort of IPI-504 on colony formation ability in SGC-7901, NCI-N87 gastric cancer and their CD44^＋stem cell like cells.Scratch test and Transwell invasion assay was applied to detect the effort of IPI-504 on migration and invasion ability in SGC-7901, NCI-N87 gastric cancer and their CD44^＋stem cell like cells.Flow cytometry was also used to detect the effect of IPI-504 on the apoptosis in SGC-7901, NCI-N87 gastric cancer and their CD44^＋stem cell like cells.Results 8%and 6%CD44^＋stem cell like cells was sorted from SGC-7901, NCI-N87 gastric cancer cells with purity 〉95%.IPI-504 could dramatically inhibit the abilities of proliferation, migration, invasion and colony formation in SGC-7901, NCI-N87 gastric cancer and their CD44^＋stem cell like cells and significantly raise the apoptosis in these cells as dose dependent.Conclusion HSP90 inhibitor IPI-504 can suppress the cells function of SGC-7901, NCI-N87 gastric cancer and their CD44^＋ stem cell like cells, and promote their apoptosis.

关 键 词：盐酸瑞他霉素 热休克蛋白90 胃癌 CD44^+干细胞样细胞 

分 类 号：R735.2[医药卫生—肿瘤]