Role of Hypoxia-inducible Factor-1α in Formation of Muttidrug Resistance Induced by Microenvironment in Hepatocellular Carcinoma  

缺氧诱导因子1α在微环境诱导的肝癌多药耐药形成过程中的作用(英文)

作　　者：罗顺峰[1] 陈孝平[1] 朱虹[1] 张必翔[1] 关剑[1] 

机构地区：[1]武汉市华中科技大学同济医学院附属同济医院肝胆胰研究所,430030

出　　处：《The Chinese-German Journal of Clinical Oncology》2006年第3期178-183,共6页中德临床肿瘤学杂志（英文版）

摘　　要：Objective： To explore the role of hypoxia-inducible factor-1α （HIF-1α） in formation of multidrug resistance （MDR） induced by microenvironment and to find a new and effective molecular target on preventing and reversing chemoresistance in hepatocellular carcinoma （HCC）. Methods： In HepG2 cells exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX, the expression of HIF-1α mRNA and protein was respectively detected using real-time fluorescent quantitative PCR and Westernblot technique and its expression localization was investigated by immunocytochemical technique. Plasmid pcDNA3/HIF-1α was transfected into HepG2 cells and then the expression of multidrug resistance related genes mdrl, multidrug resistance-associated protein 1 （MRP1） and lung resistance protein （LRP） in transfected cells was determined by the same methods. Results： In HepG2 cells respectively exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX, HIF-1α was overexpressed at mRNA and protein levels to varying degrees and translocated into nucleus. The gene expression levels of mdrl, MRP1 and LRP in HepG2 cells transfected by plasmid pcDNA3/HIF-1α were respectively increased by 2.4±0.2, 2.2±0.3 and 2.3±0.4 folds as compared with those in non-transfected HepG2 cells （all P〈0.01） and similar changes were observed in protein level. Conclusion： Microenvironmental factors around HCC could modulate the transcription of the MDR related genes by nuclear transcript factor HIF-1α, thereby conferred MDR of HCC. Up-regulation of HIF-1α expression could hold a central position in the formation of MDR of HCC induced by microenvironment. HIF-1α probably becomes a new and effective molecular target on preventing and reversing MDR in HCC.

关 键 词：hepatocellulax carcinoma multidrug resistance hypoxia-inducible factor-1α MICROENVIRONMENT 

分 类 号：R735.7[医药卫生—肿瘤]