TGF-β1调控人脑胶质瘤细胞迁移和侵袭能力的机制研究  

Mechanism of TGF-β1 Regulation of Migration and Invasion of Glioma Cells

作　　者：钞敏 刘楠 娄淼 刘竞辉 翟玉龙 王樑 涂艳阳 CHAO Min;LIU Nan;LOU Miao;LIU Jinghui;ZHAI Yulong;WANG Liang;TU Yanyang(Department of Neurosurgery,Tangdu Hospital,the Air Force Medical University,Xi′an 710038,China;Department of Experimental Surgery,Tangdu Hospital,the Air Force Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学唐都医院神经外科,西安710038 [2]空军军医大学唐都医院实验外科,西安710038

出　　处：《医学综述》2020年第9期1837-1842,1846,共7页Medical Recapitulate

基　　金：国家自然科学基金(81572983,81702458,81772661)。

摘　　要：目的探索转化生长因子-β1(TGF-β1)调控人脑胶质瘤细胞迁移和侵袭能力的机制。方法采用Western blot实验检测U251胶质瘤细胞与BV2小胶质细胞内Sox9蛋白表达水平;分别用TGF-β1处理U251、U373胶质瘤细胞20 min、40 min、1 h、2 h、4 h和6 h,采用Western blot检测Sox9蛋白表达水平的变化;采用划痕愈合实验和Transwell实验分别检测TGF-β1处理后胶质瘤细胞迁移和增殖能力的变化。结果Western blot结果显示,U251胶质瘤细胞的Sox9蛋白表达水平高于BV2小胶质细胞(1.816±0.143比0.282±0.014)(P<0.01)。TGF-β1分别处理U251胶质瘤细胞2 h和U373胶质瘤细胞20 min后,Sox9的蛋白表达水平较未处理组升高(1.570±0.061比1.347±0.024,2.125±0.188比1.490±0.036)(P<0.05)。划痕愈合实验结果显示,TGF-β1处理2 h后的U251胶质瘤细胞24 h和48 h的迁移距离大于未处理组,TGF-β1处理20 min后的U373胶质瘤细胞24 h和48 h迁移距离大于未处理组。Transwell实验显示,处理组的U251和U373胶质瘤细胞的迁移能力均大于未处理组(188.2±10.5比142.8±5.6,102.7±0.9比77.0±1.7)(P<0.01);处理组的U251和U373胶质瘤细胞的侵袭能力均较未处理组增强(117.9±2.6比74.7±4.2,123.3±6.0比69.6±2.5)(P<0.01)。结论TGF-β1可以通过在蛋白水平稳定胶质瘤细胞中Sox9的表达促进胶质瘤细胞的迁移和侵袭能力,这为胶质瘤的临床治疗提供了新思路。Objective To discover the mechanism of transforming growth factor-β1( TGF-β1) regulation of the migration and invasion of glioma cells. Methods The expression of Sox9 in U251 glioma cells and BV2 microglia cells was detected by Western blot;U251 cells and U373 glioma cells were treated with TGF-β1 for 20 min,40 min,1 h,2 h,4 h and6 h respectively,and the expression changes of Sox9 were detected by Western blot;the abilities of invasion and migration of glioma cells were disclosed by scratch-healing experiment and Transwell experiment. Results Western blot results showed that the expression level of Sox9 protein in U251 glioma cells was higher than that in BV2 microglia( 1. 816 ± 0. 143 vs0. 282 ± 0. 014)( P < 0. 01). After TGF-β1 treatment of U251 glioma cells for 2 h and U373 glioma cells for 20 min,the expression levels of Sox9 protein were higher than those of the untreated group( 1. 570 ± 0. 061 vs 1. 347 ± 0. 024,2. 125 ±0. 188 vs 1. 490 ± 0. 036)( P < 0. 05). Scratch-healing experiments showed that the migration distance of U251 glioma cells24 h and 48 h after 2 h of TGF-β1 treatment was greater than that of the untreated group,and the migration distance of U373 glioma cells 24 h and 48 h after 20 min of TGF-β1 treatment was greater than the untreated group. Transwell experiments showed that the migration ability of U251 and U373 glioma cells in the treatment group was greater than that in the untreated group( 188. 2 ± 10. 5 vs 142. 8 ± 5. 6,102. 7 ± 0. 9 vs 77. 0 ± 1. 7)( P < 0. 01);the invasion ability of U251 and U373 glioma cells in the treatment group were enhanced than the untreated group( 117. 9 ± 2. 6 vs 74. 7 ± 4. 2,123. 3 ± 6. 0 vs 69. 6 ± 2. 5)( P < 0. 01). Conclusion TGF-β1 could stabilize the expression of Sox9 protein thereby promote the invasiveness and migration of glioma cells,which offers new ideas for the clinical treatment of glioma.

关 键 词：胶质瘤 SOX9 转化生长因子-Β1 

分 类 号：R651.1[医药卫生—外科学]