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雷帕霉素在人肝癌裸鼠肝移植瘤血管形成和肿瘤进展中的作用

Effects of Rapamycin on angiogenesis and tumor progression in human hepatocellular carcinoma implantation mice

摘要:

目的 探讨雷帕霉素(RPM)在人肝癌裸鼠肝移植瘤血管形成和肿瘤发展中的作用.方法 建立人肝癌裸鼠肝移植瘤模型,使用RPM、环孢素A(CsA)进行干预治疗,采用实时定量PCR法检测移植瘤血管内皮细胞生长因子(VEGF)mRNA的表达,免疫组织化学方法和图像分析技术检测移植瘤VEGF蛋白、增殖细胞核抗原(PCNA)的表达和微血管密度(MVD),ELISA法检测外周血VEGF蛋白水平的变化.结果 (1)RPM、CsA和对照组移植瘤重量分别为(372±35)mg、(769±39)mg、(751±42)mg;RPM组移植瘤重量较对照组显著减少(P<0.01);CsA组和对照组比较无明显变化(P>0.05).(2)RPM组移植瘤VEGF mRNA、蛋白和PCNA的表达及外周血中VEGF蛋白水平较对照组显著下调(P<0.05),CsA组和对照组比较无明显差异(P>0.05).(3)RPM组移植瘤MVD较对照组显著减少(P<0.01);CsA组和对照组相比无明显变化(P>0.05).结论 RPM通过阻止肿瘤增殖,下调VEGF的表达,抑制肝癌血管形成和肿瘤进展.

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abstracts:

Objective To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma(HCC) implantation mice. Methods Tumor tissues of HCC were implanted into the liver of nude mice. Then, nude mice were treated with RPM and cyclosporine A (CsA). Real-time PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF). Immunohistochemical stain and image analysis were used to detect the protein expression of VEGF and proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. The concentration of VEGF in the peripheral blood was detected by ELISA. Results (1)The tumor weights were (372±35)mg,(769±39)mg and (751±42)mg in RPM, CsA and control group respectively. The tumor weight was significantly decreased in RPM group and no difference in CsA group compared with control group. (2) The expression of VEGF mRNA, VEGF and PCNA protein in tumor tissues and concentration of VEGF in the peripheral blood were remarkably down-regulated in RPM group compared with control group(P <0. 05) and were not remarkably different in CsA group from in control (P > 0. 05). (3) Comparing with the control, the tumor MVD was remarkably decreased in RPM group(P<0. 05),and no difference in CsA group(P>O. 05). Conclusion RPM can inhibit angiogenesis and tumor progression of HCC by down-regulated the gene and protein expression of VEGF and inhibited the growth of tumor.

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作者: 张剑 [1] 李华 [1] 汪根树 [1] 姜楠 [1] 杨扬 [1] 陈规划 [1]
第一作者: 张剑
期刊: 《中华外科杂志》2009年47卷18期 1403-1405页 MEDLINEISTICPKUCSCD
分类号: R9
栏目名称: 论著
DOI: 10.3760/cma.j.issn.0529-5815.2009.18.013
发布时间: 2009-12-07
基金项目:
国家重点基础研究发展规划(973计划) 国家自然科学基金 广东省科技计划项目
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