γ-分泌酶抑制剂通过Notch信号通路抑制人骨肉瘤细胞的迁移

γ⁃secretase inhibitor inhibits migration of human osteosarcoma cells through Notch signaling pathway

目的探究γ-分泌酶抑制剂DAPT对人骨肉瘤143B细胞和MG63细胞迁移的影响。方法首先采用免疫荧光和免疫组化分别检测MG63细胞、143B细胞和人骨肉瘤体内肺转移临床标本Notch1的表达情况,再用DAPT和Notch通路的激动剂Jagged1处理143B细胞和MG63细胞,分别用划痕试验和Transwell迁移实验观察细胞迁移变化,最后通过裸鼠体内实验检测DAPT对MG63细胞体内转移侵袭能力的影响。结果DAPT能够明显抑制143B细胞和MG63细胞划痕愈合能力以及跨膜迁移能力,MG63细胞的体内肺部转移瘤也在DAPT的作用下明显减小。结论DAPT可以抑制143B细胞和MG63细胞的体外迁移以及体内转移侵袭能力。

Objective To explore the effect ofγ⁃secretase inhibitor DAPT on the migration of human osteosarcoma 143B cells and MG63 cells.Methods Immunofluorescence and immunohistochemistry were used to detect the expression of Notch1 in MG63 cells,143B cells and clinical specimens of lung metastasis of human osteosarcoma respectively,then DAPT and Jagged1,a Notch pathway agonist,were used to treat 143B cells and MG63 cells,and the migration changes of cells were observed by wound healing assay and Transwell migration assay respectively.The effect of DAPT on the metastasis and invasion ability of MG63 cells in vivo was tested by nude mice experiments.Results DAPT could significantly inhibit the scratch healing ability and transmembrane migration ability of 143B cells and MG63 cells.The lung metastases of MG63 cells in vivo were also significantly reduced under the action of DAPT.Conclusion DAPT can inhibit the migration of 143B cells and MG63 cells in vitro and the ability of metastasis and invasion in vivo.