沙利度胺对人肝癌细胞株SMMC-7721荷瘤鼠移植瘤作用

EFFECT OF THALIDOMIDE ON HEPATOCYTE CELL LINE SMMC-7721 HUMAN LIVER CANCER MODEL IN MICE

目的研究沙利度胺对人肝癌细胞株SMMC-7721荷瘤鼠移植瘤的生长抑制作用及可能机制。方法建立肝癌细胞株SMMC-7721的荷瘤鼠模型,观察沙利度胺组与对照组瘤体变化,应用免疫组化方法测定瘤体组织中微血管密度,ELISA法测定荷瘤鼠外周血血管内皮生长因子(VEGF)表达,并采用流式细胞仪测定瘤体组织细胞凋亡指数及瘤体细胞中Caspase-3的表达。结果成功建立肝癌细胞株SMMC-7721的荷瘤鼠模型,随着皮下移植瘤的生长,在第7天以后,对照组瘤体体积渐大于沙利度胺组,且随时间延长差值增大。实验结束时沙利度胺组抑瘤率为24.6%。沙利度胺组荷瘤鼠外周血VEGF含量及瘤体组织微血管密度均显著低于对照组(t=6.563、3.586,P<0.01),瘤体组织细胞凋亡指数及Caspase-3阳性表达均显著高于对照组(t=7.356、5.147,P<0.01)。结论沙利度胺能抑制人肝癌细胞株SMMC-7721荷瘤鼠移植瘤的生长,诱导肿瘤细胞凋亡及抑制肿瘤血管形成可能为其机制,Caspase-3参与细胞的凋亡过程。

ObjectiveTo investigate the inhibitory action of thalidomide on transplanted human hepatoma cell line SMMC-7721 in mice and its possible mechanism.MethodsA mouse model bearing liver cancer cell line SMMC-7721 was created.Tumor volume in thalidomide group and control group was observed.Microvessel density（MVD） of tumor was detected byusing immunohistochemistry;VEGF protein levels by ELSIA;index of apoptosis and expression of Caspase-3 were determined by flow cytometry.ResultsA model of bearing liver cancer cell line SMMC-7721 was successfully established in mouse.Along with the growth of subcutaneously transplanted tumor,the volume of the tumor in the control group was bigger than that in the experimental group after day 7,the difference being enlarged with the extension of time.Upon completion of the experiment,the oncostatic rate in thalidomide group was 24.6%,the VEGF contents in cancer-bearing mice and MVD of the tumor were all lower than that in the control group（t=6.563,3.586;P0.01）,and the apoptotic index and the positive expression of caspase-3 were higher（t=7.356,5.147;P0.01）.ConclusionThalidomide can inhibit the growth of SMMC-7721-translated tumor in mice.Inducing apoptosis and inhibiting neovascularization are likely to be its mechanism,and caspase-3 is involved in the process of apoptosis of cells.