摘要
目的探讨鸦胆子苦醇(brusatol,BRU)对结直肠癌细胞HCT-116侵袭和迁移的影响和可能的作用机制。方法采用CCK-8法检测不同浓度的BRU对HCT-116细胞增殖能力的影响;划痕和Transwell实验检测BRU对HCT-116细胞迁移能力和侵袭能力的影响;Western blot检测BRU和ROCK抑制剂(Y27632)对HCT-116细胞中迁移侵袭相关蛋白MMP2、MMP9和RhoA、ROCK1表达的影响。结果CCK-8结果显示,经过BRU(0、2.5、5、10、20、40、80、160、320 nmol·L^(-1))处理HCT-116细胞24、48、72 h后,BRU对HCT-116细胞的抑制率明显升高,并且呈浓度和时间依赖性;划痕和Transwell实验结果显示,BRU能明显抑制HCT-116细胞的迁移和侵袭能力;Western blot结果表明,BRU和Y27632都能够明显减少HCT-116细胞中的MMP2、MMP9、RhoA和ROCK1蛋白的表达。结论BRU可能通过RhoA/ROCK1通路抑制结直肠癌细胞HCT-116的迁移和侵袭。
Aim To investigate the effect of Brusatol(BRU)on the migration and invasion of colorectal cancer HCT-116 cells and explore the underlying mechanism.Methods HCT-116 cells were treated with different concentrations of BRU and the cell inhibition was measured using CCK-8 assay.The effect of BRU on invasion and migration of HCT-116 cells was detected by Transwell assay and wound healing assay.The effects of BRU and ROCK inhibitor(Y27632)on the expression of MMP2,MMP9,RhoA and ROCK1 in HCT-116 cells were detected by Western blot.Results Detection by the CCK-8 assay revealed that with the increase of concentration BRU(0,2.5,5,10,20,40,80,160,320 nmol·L^(-1))for 24 h,48 h,and 72 h,the inhibitory rate of BRU on HCT-116 cells significantly increased in a dose and time-dependent manner;wound healing and Transwell assay indicated that BRU could significantly inhibit the migration and invasion of HCT-116 cells;Western blot results revealed that the protein levels of MMP2,MMP9,RhoA and ROCK1 were down-regulated after treatment with BRU and Y27632.Conclusion BRU inhibits the migration and invasion of colorectal cancer HCT-116 cells via RhoA/ROCK1 signaling pathway.
作者
卢睿瑾
杜玉梅
黄世莹
唐加峰
张滔
何爽
徐航
陈地龙
冉建华
李静
LU Rui-jin;DU Yu-mei;HUANG Shi-ying;TANG Jia-feng;ZHANG Tao;HE Shuang;XU Hang;CHEN Di-long;RAN Jian-hua;LI Jing(Dept of Histology and Embryology,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China;School of Public Health and Management,Chongqing Medical University,Chongqing 400016,China;Chongqing Three Gorges Medical College,Chongqing 404120,China;Laboratory of Anatomy,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第10期1360-1365,共6页
Chinese Pharmacological Bulletin
基金
重庆市教委重点项目(No KJZD-K201802701)。
