Zhang Jian, Li Hua, Wang Gen-shu, Jiang Nan, Yang Yang, Chen Gui-hua
Liver Transplantation Center, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Zhonghua Wai Ke Za Zhi. 2009 Sep 15;47(18):1403-5.
To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma (HCC) implantation mice.
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.
(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 > 0.05).
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.
研究雷帕霉素(RPM)对人肝细胞癌(HCC)种植小鼠血管生成及肿瘤进展的影响。
将HCC肿瘤组织植入裸鼠肝脏。然后,对裸鼠分别给予RPM和环孢素A(CsA)治疗。采用实时荧光定量PCR检测血管内皮生长因子(VEGF)的mRNA表达。采用免疫组织化学染色及图像分析检测VEGF和增殖细胞核抗原(PCNA)的蛋白表达,并用抗CD34抗体免疫染色的内皮细胞计数微血管密度(MVD)。采用酶联免疫吸附测定法(ELISA)检测外周血中VEGF的浓度。
(1)RPM组、CsA组和对照组的肿瘤重量分别为(372±35)mg、(769±39)mg和(751±42)mg。RPM组肿瘤重量显著降低,CsA组与对照组相比无差异。(2)与对照组相比,RPM组肿瘤组织中VEGF mRNA、VEGF和PCNA蛋白的表达以及外周血中VEGF的浓度均显著下调(P<0.05),CsA组与对照组相比无显著差异(P>0.05)。(3)与对照组相比,RPM组肿瘤MVD显著降低(P<0.05),CsA组无差异(P>0.05)。
RPM可通过下调VEGF的基因和蛋白表达抑制HCC的血管生成和肿瘤进展,并抑制肿瘤生长。