中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2012年
11期
727-730
,共4页
张斌%杨学军%于圣平%明浩朗%陈聪%任炳成%刘志峰%刘彬
張斌%楊學軍%于聖平%明浩朗%陳聰%任炳成%劉誌峰%劉彬
장빈%양학군%우골평%명호랑%진총%임병성%류지봉%류빈
神经胶质瘤%细胞运动%趋化因子
神經膠質瘤%細胞運動%趨化因子
신경효질류%세포운동%추화인자
Glioma%Cell movement%Chemotactic factors
目的 通过特异性的Rac1活性抑制剂下调Rac1的活性,探讨Rac1在基质细胞衍生因子1( SDF-1)诱导的人恶性胶质瘤U251细胞迁移和侵袭中的作用.方法 SDF-1和(或)NSC23766处理取人脑胶质瘤细胞系U251；通过细胞迁移实验和Transwell细胞侵袭实验评价不同处理组U251细胞的迁移和侵袭能力；Rac1活性实验和Western印迹分别检测不同处理组U251细胞中GTP-Rac1和总Rac1蛋白的表达水平；免疫荧光法检测不同处理组U251细胞中Rac1的表达及细胞内定位.结果 SDF-1处理组细胞迁移和侵袭能力(处理组迁移数与侵袭数分别为115.4±3.3,51.0±2.5)明显强于对照组(迁移数与侵袭数分别为64.8±2.3,28.0±2.2),P＜0.05；SDF-1对细胞内Rac1活化有明显的刺激作用(P＜0.05),并且细胞运动前端的胞膜下可见Rac1蛋白聚集.Rac1抑制剂NSC23766对SDF-1诱导的细胞迁移和侵袭有显著的抑制作用(P＜0.05)；与SDF-1处理组比较,NSC23766预处理组细胞内Rac1活性明显降低(P＜0.05),且细胞运动前端的胞膜下未见Rac1蛋白聚集.3组中总Rac1蛋白的表达水平没有明显变化(P＞0.05).结论 Rac1对SDF-1诱导的人恶性胶质瘤细胞系U251迁移和侵袭具有调控作用,抑制Rac1活化可能成为治疗恶性胶质瘤的新的治疗策略.
目的 通過特異性的Rac1活性抑製劑下調Rac1的活性,探討Rac1在基質細胞衍生因子1( SDF-1)誘導的人噁性膠質瘤U251細胞遷移和侵襲中的作用.方法 SDF-1和(或)NSC23766處理取人腦膠質瘤細胞繫U251；通過細胞遷移實驗和Transwell細胞侵襲實驗評價不同處理組U251細胞的遷移和侵襲能力；Rac1活性實驗和Western印跡分彆檢測不同處理組U251細胞中GTP-Rac1和總Rac1蛋白的錶達水平；免疫熒光法檢測不同處理組U251細胞中Rac1的錶達及細胞內定位.結果 SDF-1處理組細胞遷移和侵襲能力(處理組遷移數與侵襲數分彆為115.4±3.3,51.0±2.5)明顯彊于對照組(遷移數與侵襲數分彆為64.8±2.3,28.0±2.2),P＜0.05；SDF-1對細胞內Rac1活化有明顯的刺激作用(P＜0.05),併且細胞運動前耑的胞膜下可見Rac1蛋白聚集.Rac1抑製劑NSC23766對SDF-1誘導的細胞遷移和侵襲有顯著的抑製作用(P＜0.05)；與SDF-1處理組比較,NSC23766預處理組細胞內Rac1活性明顯降低(P＜0.05),且細胞運動前耑的胞膜下未見Rac1蛋白聚集.3組中總Rac1蛋白的錶達水平沒有明顯變化(P＞0.05).結論 Rac1對SDF-1誘導的人噁性膠質瘤細胞繫U251遷移和侵襲具有調控作用,抑製Rac1活化可能成為治療噁性膠質瘤的新的治療策略.
목적 통과특이성적Rac1활성억제제하조Rac1적활성,탐토Rac1재기질세포연생인자1( SDF-1)유도적인악성효질류U251세포천이화침습중적작용.방법 SDF-1화(혹)NSC23766처리취인뇌효질류세포계U251；통과세포천이실험화Transwell세포침습실험평개불동처리조U251세포적천이화침습능력；Rac1활성실험화Western인적분별검측불동처리조U251세포중GTP-Rac1화총Rac1단백적표체수평；면역형광법검측불동처리조U251세포중Rac1적표체급세포내정위.결과 SDF-1처리조세포천이화침습능력(처리조천이수여침습수분별위115.4±3.3,51.0±2.5)명현강우대조조(천이수여침습수분별위64.8±2.3,28.0±2.2),P＜0.05；SDF-1대세포내Rac1활화유명현적자격작용(P＜0.05),병차세포운동전단적포막하가견Rac1단백취집.Rac1억제제NSC23766대SDF-1유도적세포천이화침습유현저적억제작용(P＜0.05)；여SDF-1처리조비교,NSC23766예처리조세포내Rac1활성명현강저(P＜0.05),차세포운동전단적포막하미견Rac1단백취집.3조중총Rac1단백적표체수평몰유명현변화(P＞0.05).결론 Rac1대SDF-1유도적인악성효질류세포계U251천이화침습구유조공작용,억제Rac1활화가능성위치료악성효질류적신적치료책략.
Objective To explore the role of Rac1 in the SDF-1-induced migration and invasion of glioma cells with a specific Rac1 inhibitor.Methods Human glioma cell lines U251 treated with SDF-1 or/and specific Rac1 inhibitor were used.The migration and invasion capacities of cells in 2D cell migration/3D invasion assay were assessed.Western blot was employed to detect the levels of Rac1 and GAPDH in cell lysates and the Rac1 activity measured by Rac1 activation assays.Immunofluorescence was used to identify the expression and intracellular location of Rac1 in U251 cells.Results SDF-1 significantly increased the migration and invasion capacities of U251 cells (P ＜ 0.05 ).The stimulation of SDF-1 boosted the activity of Rac1 versus the unstimulated cells (P ＜ 0.05 ).And Rac1 was recruited to protruding edge in SDF-1-stimulated cells. Inhibition of Rac1 with specific Rac1 inhibitor decreased the migration and invasion capacities of SDF-1-induced U251 cells(P ＜ 0.05 ).In comparison with the SDF-1 treated group,the activity of Rac1 significantly decreased (P ＜ 0.05 )and the recruitment of Rac1 to protruding edge significantly decreased in the NSC23766 pre-treated group.Conclusions This study provides novel evidence that Rac1 modulates the SDF-1-induced migration and invasion of glioma cells.It suggests that the inhibition of Rac1 activation may be a new therapeutic target for glioma.
