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

摘要

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 for-mation 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.%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、NCI－N87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。