内质网应激对胃癌细胞迁移与侵袭的影响

Effect of endoplasmic reticulum stress on gastric cancer cell migration and invasion

目的:探讨内质网应激(endoplasmic reticulum stress,ERS)对胃癌细胞迁移及侵袭能力的影响及其机制.方法:5μg/mL衣霉素处理胃癌细胞系SGC7901或BGC823 0、12、24及36 h,Western blot检测各时间点葡萄糖调节蛋白78(glucoseregulated protein 78,GRP78)、金属基质蛋白酶9(matrix metalloproteinase 9,MMP9)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达;划痕实验检测衣霉素处理不同时间后对胃癌细胞迁移能力的影响,各时间点均设未加药对照组;Transwell侵袭实验检测衣霉素处理不同时间后对胃癌细胞侵袭能力的影响,各时间点均设未加药对照组.结果:与相应的0 h组相比,衣霉素处理胃癌细胞系SGC7901或BGC823 12、24及36 h后,GRP78、MMP9及VEGF的蛋白表达量均明显增加(P<0.05);衣霉素处理12、24及36 h后,胃癌细胞的划痕愈合度及胃癌细胞侵袭到Transwell下室的细胞数均明显高于0 h组(P<0.05).结论:ERS可上调MMP9及VEGF,促进胃癌细胞的迁移与侵袭.

AIM： To investigate the effect of endoplasmic reticulum stress（ERS） on gastric cancer cell migration and invasion. METHODS： Gastric cancer BGC823 or SGC7901 cells were treated with tunicamycin（TM） for 0, 12, 24 and 36 h. The expression of glucose-regulated protein 78（GRP78）, matrix metalloproteinase 9（MMP9） and vascular endothelial growth factor（VEGF） was analyzed using Western blot. Wound healing assay was used to detect the migrating ability of gastric cancer cells at each time point with or without TM treatment. Transwell assay was employed to examine invasive ability of gastric cancer cells at each time point with or without TM treatment. RESULTS： Compared with baseline values, the expression of GRP78, MMP9 and VEGF in gastric cancer cells was significantly increased after treatment with TM for 12, 24 or 36 h（P 〈 0.05）. Wound healing ability of gastric cancer cells treated with TM for 12, 24 or 36 h was much stronger than that in the 0 h group（P 〈 0.05）. The number of gastric cancer cells invading to the lower chamber increased after TM treatment for 12, 24 or 36 h（P 〈 0.05）. CONCLUSION： ERS promotes gastric cancercell migration and invasion probably via upregulation of MMP9 and VEGF expression.