C75对肝癌细胞侵袭转移的影响及其机制

Effect of C75 on invasion and migration of hepatic cancer cells and its mechanism

目的观察C75对肝癌MHCC97H细胞侵袭转移的作用,并探讨其作用机制。方法通过划痕实验和Transwell小室检测C75对肝癌MHCC97H细胞迁徙和侵袭的影响。采用Western blot的方法探讨C75对MMP-2、MMP-9及其抑制物TIMP-2、TIMP-1表达的影响。采用明胶酶谱的方法检测C75对MMP-2和MMP-9蛋白酶活性的影响。结果 C75能够明显抑制MHCC97H细胞迁徙能力和侵袭能力;C75能够抑制MHCC97H细胞中MMP-2、MMP-9的表达水平及酶活性,且能够增高TIMP-1和TIMP-2的表达水平。结论 C75能够抑制肝癌细胞MHCC97H的迁徙和侵袭能力。这种抑制作用可能与其对MMP/TIMP的平衡调节相关。

Objective To investigate the effect of a FASN inhibitor C75 on MHCC97H cell invasion and migration,and to explore its molecular mechanisms.Methods The anti-metastatic effect of C75 was determined using wound healing assay and Transwell invasion model.The expression of MMP-2,MMP-9,TIMP-1 and TIMp-2 protein in MHCC97H cells was determined by Western blot.The activities of MMP-2 and MMP-9 were determined by gelatin-zymography.Results The migration and invasion of MHCC97H cells were markedly suppressed by C75 in a dose-dependent manner.After treatment with C75 for 24 h,the expression of MMP-2 and MMP-9,and proteinase activities decreased.Meanwhile,the expression of TIMP-1 and TIMP-2 were increased in a dose-dependent fashion.Conclusion These findings suggest that C75 preferentially inhibits HCC invasion by regulating the synthesis of proteinases and their inhibitors.C75 may be a potential novel therapeutic agent for HCC.