兰州大学机构库 >学院待认领
IGF-IR在人的不同肝细胞系上表达和定位及阻断IGF-IR对HepG2细胞生长影响的实验研究
Alternative TitleExpression and Localization of IGF-I Receptor in Human Different Hepatocellular Lines and Effect of Anti-IGF-I Receptor Monoclonal Antibody on Growth of HepG2 Cells
王晓鹏
Thesis Advisor张有成 ; 寇治民
2005-05-31
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword胰岛素样生长因子 受体 表达 单克隆抗体 增殖
Abstract目的:了解胰岛素样生长因子I型受体(IGF-IR)在人肝癌细胞株HepG2及正常人肝细胞株Chang Liver上的表达和定位;观察胰岛素样生长因子I型受体单克隆抗体(αIR3)对HepG2细胞生长的生物学作用。 方法: 免疫组织化学法检测HepG2及Chang Liver细胞的IGF-IR表达;四甲基偶氮唑蓝(MTT)法检测αIR3对HepG2细胞增殖的影响;流式细胞术分析αIR3对HepG2细胞细胞周期及凋亡的影响;透射电镜观察αIR3作用于HepG2细胞后的形态学变化。 结果: 与Chang Liver细胞相比,HepG2细胞膜高表达IGF-IR;αIR3 (0.1ug/ml)作用48h于HepG2细胞,其相对生长指数(GI)为103.41%,与对照组相比有显著差异性 (P<0.01),αIR3(0.2~4.0ug/ml)作用48h HepG2细胞,其GI分别为95% ~70.51%,且呈时间-剂量依赖关系,与对照组相比有显著差异性(P<0.05 或P<0.01);αIR3(0.5~2.0ug/ml)能增加G0/G1期HepG2细胞比值、减少S期HepG2细胞比值,但对G2/M期HepG2细胞比值无明显影响,同时使细胞凋亡率也增高(P<0.01)。透射电镜观察到细胞凋亡现象。 结论:肝癌细胞的恶性表型与IGF-IR的过度表达有关;在一定浓度范围,胰岛素样生长因子I型受体单克隆抗体αIR3可以通过阻断IGF-IR抑制HepG2的增殖、诱导其凋亡。
Other AbstractObjective To study the expression level and localization of IGF-I receptor (IGF-IR) in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-I receptor monoclonal antibody (αIR3) on the growth of HepG2 cells. Methods The expression of IGF-IR in HepG2 cells and Chang liver cells was detected by immunohistochemistry method. The influence of αIR3 on proliferation and apoptosis were examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and electron microscopy method, respectively. The flow cytometry(FCM) was applied for the analysis of the cell cycle and apoptosis. Results Compared with Chang liver cells, the expression level of IGF-1R, which was located in the cell membranes of both cells , was higher in the cell membranes of HepG2 cells. The cell growth index (GI) of HepG2 cells treated for 48h in vitro by 0.1ug/ml αIR3 was 103.41% , and significantly higher than that of control group(P<0.01). Treated with αIR3 at final concentration ranging from 0.2ug/ml to 4.0ug/ml,the GI of HepG2 cells was 97.63% to 70.51% in a dose- and time-dependent manner, lower than that of control group (P<0.05 or P<0.01).At concentration of 0.5ug/ml to 2.0ug/ml, αIR3 treatment increased the proportion of G0/G1 phase cells and decreased that of S phase cells significantly (P<0.01), but there was no significant change in the proportion of G2/M phase cells. The rate of apoptosis of the cells were obviously increased (P<0.01). The apoptosis of the cell were observed under electron microscopy. Conclusions The malignant cell phenotype of human heptatocarcinorma cell is related to overexpression of IGF-IR; The blockage of the IGF-ⅠR with αIR3 may contribute to the inhibition of proliferation and the induction of apoptosis in HepG2 cells.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224084
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
王晓鹏. IGF-IR在人的不同肝细胞系上表达和定位及阻断IGF-IR对HepG2细胞生长影响的实验研究[D]. 兰州. 兰州大学,2005.
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