PDF(Pubmed)
Abstract：
The aim of the present study was to investigate the impact and mechanism of high mobility group box 1 (HMGB1) on the regulation of cell migration and invasion in A2780/DDP cisplatin-resistant ovarian cancer cells. After transfecting small interfering (si)RNA-HMGB1 into A2780/DDP cells, Transwell migration and invasion assays were conducted to assess alterations in the cell migratory and invasive abilities. Additionally, western blotting analyses were performed to examine changes in HMGB1, phosphorylated (p)-GSK-3β, GSK-3β, E-cadherin and vimentin expression levels. The results of the present study demonstrated that the migratory and invasive abilities of A2780/DDP cells were significantly higher compared with those of A2780 cells. Additionally, the expression levels of HMGB1, p-GSK-3β and the mesenchymal phenotype marker, vimentin, in A2780/DDP cells were significantly elevated relative to the levels in A2780 cells. Conversely, the expression level of the epithelial phenotype marker, E-cadherin, was markedly decreased compared with that in A2780 cells. Following transfection of A2780/DDP cells with siRNA-HMGB1, there was a significant reduction in the rate of cell migration and invasion. Simultaneously, the expression levels of HMGB1, p-GSK-3β and vimentin were downregulated while the level of E-cadherin was upregulated. It was therefore concluded that the high expression of HMGB1 in A2780/DDP cells enhanced the cell migration and invasion abilities by facilitating epithelial to mesenchymal transition via GSK-3β.
摘要：
本研究的目的是探讨高迁移率族蛋白1（HMGB1）对A2780/DDP顺铂耐药卵巢癌细胞迁移和侵袭的影响及其机制。将小干扰（si）RNA-HMGB1转染入A2780/DDP细胞后，进行Transwell迁移和侵袭测定以评估细胞迁移和侵袭能力的改变。此外,进行蛋白质印迹分析以检查HMGB1，磷酸化（p）-GSK-3β，GSK-3β,E-钙粘蛋白和波形蛋白表达水平。本研究结果表明，A2780/DDP细胞的迁移和侵袭能力明显高于A2780细胞。此外,HMGB1、p-GSK-3β和间充质表型标记物的表达水平,波形蛋白,A2780/DDP细胞中的水平相对于A2780细胞中的水平显著升高。相反，上皮表型标志物的表达水平，E-cadherin,与A2780细胞相比明显减少。在用siRNA-HMGB1转染A2780/DDP细胞后,细胞迁移和侵袭率显著降低。同时,HMGB1，p-GSK-3β和波形蛋白的表达水平下调，而E-cadherin的表达水平上调。因此得出结论，HMGB1在A2780/DDP细胞中的高表达通过促进GSK-3β的上皮向间充质转化来增强细胞的迁移和侵袭能力。
