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作 者:赵志成[1] 庄莉[1] 贾长库[1] 郑树森[1]
机构地区:[1]浙江大学医学院附属第一医院肝胆胰外科,卫生部多器官移植重点实验室,浙江省器官移植重点实验室,浙江杭州310003
出 处:《中国病理生理杂志》2010年第4期713-720,共8页Chinese Journal of Pathophysiology
基 金:浙江省中医药课题资助项目(No.2005C175);浙江省中医药重大课题资助项目(No.2007ZA014)
摘 要:目的:研究表没食子儿茶素没食子酸酯(EGCG)抑制肝癌生长的分子机制。方法:采用MTT方法观察EGCG对HepG2细胞株增殖的影响;利用体外厌氧培养技术,通过不同剂量的EGCG进行干预,检测肝癌细胞HIF-1α/VEGF的基因转录和蛋白表达;将肝癌细胞种植于裸鼠体内,观察EGCG对肿瘤生长的抑制作用,并且测定HIF-1α/VEGF的表达。结果:体外试验显示EGCG对肝癌细胞株HepG2的增殖有明显抑制作用;明显下调HIF-1α/VEGF蛋白的表达,而对HIF-1α基因转录影响不大;裸鼠体内试验中观察到EGCG对肿瘤生长有明显抑制作用,抑制率达39.8%±5.1%。结论:EGCG可明显抑制肝癌细胞的增殖,干预HIF-1α/VEGF信号转导通路可能是其抑制肿瘤生长的主要机制之一。AIM:To study the molecular mechanism of EGCG on inhibiting the growth of hepatic carcinoma. METHODS: The proliferation of hepatic cell line HepG2 cultured with different doses of EGCG was studied by MTT and suspension/adherence methods. The effect of EGCG on the expression of HIF-1α/VEGF at mRNA and protein levels in vitro and in vivo was evaluated by RT-PCR and Western blotting,respectively. The inhibition of EGCG on the growth of tumor implanted into athymic nude mice was also observed. RESULTS: The proliferation of hepatic cell line HepG2 was inhibited by EGCG in a dose-dependent manner. The expression of HIF-1α/VEGF was suppressed markedly by EGCG at protein level. However,the inhibitory effect of EGCG on the mRNA expression was only observed on VEGF,not on HIF-1α. In the animal experiment,the implanted tumor growth was inhibited by 39.8%±5.1%. CONCLUSION: EGCG suppresses the hepatic carcinoma cell growth,and interrupts the HIF-1α/VEGF signaling pathway significantly,indicating a fundamental mechanism of EGCG for inhibiting tumor growth.
关 键 词:表没食子儿茶素没食子酸酯 肝肿瘤 缺氧诱导因子-1 血管内皮生长因子
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