FXR激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响

目的:探讨研究法尼酯x受体(FXR)激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响。方法:选取人肝癌细胞系Hep G2进行体外培养,将细胞悬液接种于BALB/c裸鼠皮下。裸鼠成瘤后,随机分为两组,分别腹腔注射DMSO和GW4064。一周后,处死动物取肿瘤组织,通过免疫组织化学法检测肿瘤组织中Ki-67和CD31的表达,同时计数肿瘤组织中的微血管密度(CD31-MVD);Western blot法检测其FXR和白介素-8(IL-8)的蛋白表达。结果:与对照组相比,FXR激动剂GW4064处理组的肿瘤组织中FXR的蛋白表达量明显增高,微血管密度CD31-MVD值显著降低,同时Ki-67、IL-8及CD31的表达水平均显著降低。结论:FXR激动剂GW4064能显著增加FXR的表达,抑制裸鼠肝癌细胞移植瘤的增殖及新生血管的形成。

Effect of FXR Agonist GW4064 on the Proliferation and Angiogenesis of HCC Cells in Nude Mice

Objective:To investigate the effect of FXR agonist GW4064 on the proliferation and angiogenesis of hepatocellular carcinoma (HCC)cells in BALB/c nude mice.Methods:Human hepatocellular carcinoma cell line HepG2 were cultured in vitro, then implanted subcutaneously in nude mice. When the subcutaneous xenograft was formed, the nude mice were randomly divided into a control group and an experimental group, which were injected with DMSO and GW4064 respectively. After one week, the tumor was separated, the expression of Ki67 and CD31 were detected by immunohistochemical(IHC) method, the microvessel density (CD31-MVD) of tumors were calculated, and the expression of FXR and IL-8 were detected by Western blot assays.Results:Compared with control group, the expression of FXR increased significantly, the microvessel density CD31-MVD value decreased significantly, while the expression level of Ki-67, IL-8 and CD31were significantly inhibited in GW4064 group.Conclusion:FXR agonist GW4064 may stimulate the expression of FXR thereby inhibiting the cell proliferation and tumor angiogenesis of hepatocellular carcinoma cell xenografts in nude mice.