CAJ | 학술논문

目的：探讨肽基脯酰胺顺反异构酶Pin1（peptidyl-prolyl isomerase 1）抑制剂胡桃醌（Juglone）对胶质瘤细胞U-87 MG迁移、侵袭能力的影响并探讨相关机制。方法胶质瘤细胞株U-87 MG经0、0.8、1.6和3.2μmol·L-1胡桃醌处理后，以细胞划痕实验检测细胞迁移能力，transwell小室实验检测细胞侵袭能力，western blot法检测β-链蛋白（β-catenin）、血管内皮细胞生长因子（vascular endothelial growth factor, VEGF）、基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）和基质金属蛋白酶-9（matrix metalloproteinase-9，MMP-9）的蛋白表达水平。结果细胞划痕实验结果显示1.6μmol·L-1和3.2μmol·L-1胡桃醌组U-87 MG细胞划痕创面愈合率分别为46.04%±6.25%和30.05%±13.35%，与0μmol·L-1组比较明显下降（P<0.05）；transwell小室实验结果显示1.6μmol·L-1和3.2μmol·L-1胡桃醌组穿膜细胞数平均为（103.67±5.69）个和（77.33±7.77）个，与0μmol·L-1组比较明显减少（P<0.05）；western blot实验结果显示胡桃醌可显著下调U-87 MG细胞β-catenin、VEGF、MMP-2和MMP-9蛋白表达水平，作用随浓度增加而增大。结论胡桃醌可通过下调β-catenin及其下游MMP-2、MMP-9和VEGF的蛋白表达而抑制胶质瘤细胞迁移、侵袭能力。
목적：탐토태기포선알순반이구매Pin1（peptidyl-prolyl isomerase 1）억제제호도곤（Juglone）대효질류세포U-87 MG천이、침습능력적영향병탐토상관궤제。방법효질류세포주U-87 MG경0、0.8、1.6화3.2μmol·L-1호도곤처리후，이세포화흔실험검측세포천이능력，transwell소실실험검측세포침습능력，western blot법검측β-련단백（β-catenin）、혈관내피세포생장인자（vascular endothelial growth factor, VEGF）、기질금속단백매-2（matrix metalloproteinase-2，MMP-2）화기질금속단백매-9（matrix metalloproteinase-9，MMP-9）적단백표체수평。결과세포화흔실험결과현시1.6μmol·L-1화3.2μmol·L-1호도곤조U-87 MG세포화흔창면유합솔분별위46.04%±6.25%화30.05%±13.35%，여0μmol·L-1조비교명현하강（P<0.05）；transwell소실실험결과현시1.6μmol·L-1화3.2μmol·L-1호도곤조천막세포수평균위（103.67±5.69）개화（77.33±7.77）개，여0μmol·L-1조비교명현감소（P<0.05）；western blot실험결과현시호도곤가현저하조U-87 MG세포β-catenin、VEGF、MMP-2화MMP-9단백표체수평，작용수농도증가이증대。결론호도곤가통과하조β-catenin급기하유MMP-2、MMP-9화VEGF적단백표체이억제효질류세포천이、침습능력。
Objective To investigate the effects and mechanisms of pin1(peptidyl-prolyl isomerase 1) inhibitor ju?glone on migration and invasion in glioma cell line U-87 MG. Methods Glioma cells were treated with juglone at 0, 0.8, 1.6 and 3.2μmol·L-1. Wound-healing assay and invasion assay were performed to examine the inhibitory activity of ju?glone on glioma cell line U-87 MG. Western blot was used to analyze the protein expression of β-catenin, VEGF, MMP-2 and MMP-9. Results The wound-healing assay showed that the wound-healing rate in juglone-treated groups was 46.04%±6.25%and 30.05%±13.35%at concentrations of 1.6μmol·L-1 and 3.2μmol·L-1 , repectively. Juglone treat?ment significantly reduced the wound-healing rate compared with controls (P<0.05). Transwell invasion assay showed that the number of invaded cells in juglone–treated groups was 103.67 ± 5.69 and 77.33 ± 7.77 at the concentrations of 1.6μmol·L-1 and 3.2μmol·L-1 , respectively. Juglone treatment significantly reduced cell invasion compared with con?trols (P<0.05). Treatment with juglone significantly down-regulated the expression levels ofβ-catenin, VEGF, MMP-2 and MMP-9 in U-87 MG cells in a dose-dependent manner. Conclusion The present data suggests that juglone has a significant inhibitory action on cell migration and invasion through down-regulation of theβ-catenin and its downstream VEGF, MMP-2 and MMP-9 protein expressions in glioma cell line U-87 MG.