达沙替尼(dasatinib)通过上调上皮钙黏蛋白表达抑制SK-Hep-1人肝癌细胞的增殖、分散和迁移  

Multi-target kinase inhibitor dasatinib inhibits cell proliferation,dissociation andm igration via up-regulating E-cadherin expression in SK-Hep-1 human hepatocellular cancer cells

作　　者：刘畅[1] 裴晋红[1] 穆秀丽 于保锋 LIU Chang;PEI Jinhong;MU Xiuli;YU Baofeng(Department of Biochemistry and Molecular Biology,Changzhi Medical College,Changzhi 046000;Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]长治医学院基础部生物化学与分子生物学教研室,山西长治046000 [2]山西医科大学基础医学院生物化学与分子生物学教研室,山西太原030001

出　　处：《细胞与分子免疫学杂志》2021年第9期801-807,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：山西省自然科学基金(201901D111190,2015011113);山西省重点研发计划(国际合作)项目(201703D421023);长治医学院博士科研启动基金(BS202007)。

摘　　要：目的研究多靶点激酶抑制剂达沙替尼(dasatinib)对SK-Hep-1人肝癌细胞增殖、黏附和迁移能力的影响及机制。方法先采用dasatinib处理SK-Hep-1、Bel-7402、SNU-423、SNU-387、Huh-7肝癌细胞,噻唑蓝(MTT)法检测dasatinib对肝癌细胞存活和增殖的影响,筛选出对dasatinib敏感的肝癌细胞;培养SK-Hep-1细胞,采用(0.5、1、2)μmol/L dasatinib处理,对照组采用二甲基亚砜(DMSO)处理。采用细胞缓慢聚集实验和分离实验检测dasatinib对SK-Hep-1肝癌细胞间同质黏附力的影响,划痕实验观察dasatinib对肝癌细胞迁移能力的影响;Western blot法检测dasatinib对上皮钙黏蛋白(E-cadherin)表达的影响。结果MTT实验证明dasatinib明显抑制肝癌细胞增殖,且SK-Hep-1细胞对dasatinib最敏感。dasatinib处理促进SK-Hep-1细胞聚集,抑制细胞分散和迁移,上调肝癌细胞E-cadherin表达。结论Dasatinib通过上调E-cadherin表达促进SK-Hep-1肝癌细胞聚集和黏附,抑制细胞增殖、分散和迁移。Objective To investigate the effects of dasatinib(a multi-target kinase inhibitor)on the proliferation,adhesion and migration ability of SK-Hep-1 human hepatocellular cancer cells and the underlying mechanism.MethodsSK-Hep-1,Bel-7402,SNU-423,SNU-387 and Huh-7 hepatocellular cancer cells were treated with dasatinib.Then MTT assay was used to detect the effect of dasatinib on the survival and proliferation of cancer cells,and the sensitive cells were obtained.SK-Hep-1 cells were cultured and treated with(0.5,1,2)μmol/L dasatinib,and the control group was treated with DMSO.Slow aggregation assay and dissociation assay were used to detect the effects of dasatinib on the adhesion ability of SK-Hep-1 cells.Wound healing assay was applied to observe the effect of dasatinib on the migration ability of the cancer cells.Western blotting was performed to detect the effect of dasatinib on the expression of E-cadherin.Results MTT assay showed that the proliferation of the liver cancer cells was obviously inhibited by dasatinib and SK-Hep-1 was the most sensitive cells to dasatinib.Dasatinib promoted the aggregation of SK-Hep-1 cells,inhibited cell dissociation and migration,and up-regulated E-cadherin expression.Conclusion Dasatinib can promote the aggregation and adhesion of SK-Hep-1 cells,and inhibit cell proliferation,dissociation and migration via up-regulating E-cadherin expression.

关 键 词：达沙替尼(dasatinib) SK-Hep-1细胞 上皮钙黏蛋白(E-cadherin) 黏附 迁移 

分 类 号：R965[医药卫生—药理学] Q279[医药卫生—药学]