多药耐药基因及缺氧诱导因子-1α在食管癌组织中的表达及其临床意义_临床医学论文.docVIP

多药耐药基因及缺氧诱导因子-1α在食管癌组织中的表达及其临床意义_临床医学论文 多药耐药基因及缺氧诱导因子-1α在食管癌组织中的表达及其临床意义_临床医学论文 作者：张广健 高蕊 付军科 金鑫 张明鑫 王健生 【摘要】 目的分析食管癌多药耐药基因(MDR1)及缺氧诱导因子1α(HIF-1α)的表达的相关性及探讨其与临床病理间的关系。方法应用实时定量PCR(QRT-PCR)及Western blot对34例食管癌及癌旁组织标本的MDR1及HIF-1α表达水平进行检测。结果34例食管癌组织的MDR1表达显著低于癌旁组织(0.05)，但高于正常组织(0.05)。而HIF-1α在癌组织的表达水平则显著高于癌旁组织(0.05)。两基因表达水平存在正相关关系(0.01)。HIF-1α、MDR1表达均与食管癌的分化程度呈正相关。结论MDR1、HIF-1α的表达在食管癌及癌旁组织中均明显上调。HIF-1α可能通过诱导MDR1表达导致食管癌化疗耐药。 【关键词】 多药耐药基因;缺氧诱导因子;食管癌 　ABSTRACT: ObjectiveTo explore the expressions of multidrug resistance gene (MDR1) and hypoxia-inducible factor 1α (HIF-1α) in human esophageal cancer and the correlation between them as well as clinical pathological factors.MethodsBiopsy samples from 34 esophageal cancer patients were used. The mRNA and protein levels of MDR1 and HIF-1α were measured by quantitative reverse transcription polymerase chain reaction (QRT-PCR) and Western blot analysis, respectively.ResultsThe MDR1 expression level of cancerous tissues was significantly lower than that of tissues adjacent to the carcinoma site (0.05). However, the level of HIF-1α expression in cancer tissues was much higher than that in the paratumor tissues (0.05). There was a positive correlation between HIF-1α and MDR1 expressions. HIF1α and MDR1 levels were both correlated with clinical stage of esophageal cancer.　　ConclusionMDR1 and HIF-1α are over-expressed in esophageal cancer and in tissues adjacent to the carcinoma site simultaneously. The modulation of MDR1 expression is probably dependent upon the expression of HIF-1α. 　　KEY WORDS: multidrug resistance gene (MDR1); hypoxia-inducible factor 1α (HIF-1α); esophageal cancer 　　食管癌是我国最常见的恶性肿瘤之一，预后较差。50%～60%的患者就诊时已有远处转移，中位生存期4～8个月。虽然近年来化疗方案的改善可以使中晚期食管癌的化疗有效率得到提高，但总的5年生存率仍低于20%[1]。化疗耐药(multidrug resistance, MDR)是导致食管癌药物治疗失败的根本原因。因此，研究食管癌MDR机制是提高其化疗效果最关键一步。缺氧是实体肿瘤生长的微环境特征之一。肿瘤内部总处于相对缺血缺氧的微环境。缺氧诱导因子-1(hypoxia-inducible factor 1, HIF-1)是缺氧环境下被激活的重要转录因子，其受氧调节的亚基HIF-1α对化疗耐药基因MDR1表达的调控作用受到越来越多的关注。但是，两者的相关性至今未在食管癌组织中得到证实。本文即在mRNA及蛋白水