EGCG对人肝癌细胞株HepG2裸鼠移植瘤COX-2、VEGF和bFGF表达的调控  

Regulation of EGCG on Expression of COX-2, VEGF, and bFGF in Nude Mice Xenogrfts Tumor of Human HepG2 Cells

作　　者：周薇[1] 戴奇刚[2] 邓鑫[3] 荣孪君[1] 王英桂[1] 

机构地区：[1]广东药学院附属第二医院病理科,广东广州510300 [2]广东药学院附属第一医院放疗科,广东广州510080 [3]广西中医学院附属瑞康医院科教科,广西南宁530011

出　　处：《中山大学学报（医学科学版）》2013年第3期364-370,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广西壮族自治区科学技术厅青年基金(桂科青0832056)

摘　　要：【目的】探讨表没食子儿茶素没食子酸脂EGCG对人肝癌细胞株HepG2裸鼠移植瘤生长和肿瘤血管生成的抑制作用及EGCG对移植瘤环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)和碱性成纤维生长因子(bFGF)表达的调控。【方法】将肝癌细胞HepG2种植至裸鼠背部皮下,10 d后开始用不同浓度EGCG治疗,38 d后处死。观测裸鼠移植瘤的体积和质量。并采用间接免疫流式细胞术和Western Blot法检测移植瘤COX-2、VEGF和bFGF的表达,用免疫组化法检测微血管密度(MVD)。【结果】①生理盐水组切除的移植瘤平均体积和质量分别是(1174.6±793.5)mm3和(0.572±0.138)g,EGCG 50 mg/kg组分别为(649.3±100.8)mm3和(0.340±0.066)g,两组比较差异有统计学意义(P<0.05)。EGCG 50 mg/kg组抑瘤率为40.56%。②生理盐水对照组和EGCG 50mg/kg组的MVD值分别为23.24±1.76和14.27±1.25,两组差异有统计学意义(P<0.01);间接免疫荧光流式细胞术和Western Blot检测结果提示EGCG呈浓度依赖性地抑制人肝癌细胞HepG2移植瘤中COX-2、VEGF和bFGF的表达。【结论】EGCG具有抑制人肝癌裸鼠移植瘤生长的作用;同时能抑制肝癌移植瘤内新生血管内皮细胞的生长,其机制可能与抑制COX-2的表达以及由此引起的VEGF和bFGF蛋白表达降低有关。[Objective] To investigate the inhibitory effects of （-）-Epigallocatechin-3-gallate （EGCG） on growth and tumor angiogenesis and regulations of EGCG on expression of COX-2 （cyclooxygenase-2）,VEGF （vascular endothelial growth factor）,and bFGF （basic fibroblast growth factor） in nude mice xenogrfts tumor of Human HepG2 Cells.[Methods] HepG2 cells were transplanted into the dorsal subcutaneous tissue of athymic nude mice.The mice were treated with different concentrations of EGCG 10 days after transplantation,and were killed after 38 days.Tumor volume and weight were measured.Expression of COX-2,VEGF,and bFGF were detected by indirect immunofluorescence flow cytometry assay and Western blot and microvessel density （MVD） using immunohistochemical methods.[Results] The average tumor volume was significantly smaller and the average tumor weight was significandy lighter in EGCG 50mg/kg group than in control group [（1174.6 ± 793.5）mm3 vs （649.3 ± 100.8） mm3 and （0.572 ± 0.138）g vs （0.340 ± 0.066）g,P 〈 0.05].The inhibitory rate of tumor growth was 40.56%.MVD values of the saline control group and the group of EGCG 50 mg/kg were （23.24 ± 1.76） and （14.27 ± 1.25）,the difference was statistically significant （P 〈 0.01）;indirect immunofluorescence flow cytometry and Western Blot analysis results suggest that EGCG was concentration-dependently inhibited HepG2 cells transplanted tumors in the expression of COX-2,VEGF and bFGF.[Conclusions]EGCG inhibits the growth and angiogenesis of HepG2 cell xenogrfts in small nude mice.It＇s mechanism may be related to the inhibition of COX-2 expression and the resulting VEGF and bFGF protein expression lower them.

关 键 词：HepG2细胞 裸鼠移植瘤 新生血管生成 COX-2 VEGF bFGF 

分 类 号：R73-3[医药卫生—肿瘤]