9-顺式维甲酸协同-干扰素下调神经母细胞瘤细胞MYCN和MDR1基因mRNA表达的实验研究  

The study of 9-cis retinoic acid and gamma-interferon synergize in down-regulating MYCN,MDR1 mRNA expression of human neuroblastoma cell

作　　者：孙福涛[1] 王兴 张文同[3] 

机构地区：[1]临沂市人民医院儿外科,山东临沂276003 [2]临沭人民医院外科,山东临沂276003 [3]山东大学齐鲁医院儿外科,山东济南250012

出　　处：《泰山医学院学报》2011年第1期1-4,共4页Journal of Taishan Medical College

基　　金：临沂市科学技术发展计划项目;项目编号为080103001

摘　　要：目的测定9-顺式维甲酸(9-cis retinoic acid,9-cis RA)联合γ-干扰素(gamma-interferon,γ-IFN)在体外诱导神经母细胞瘤(neuroblastoma,NB)SK-N-SH细胞分化过程中MYCN和MDR1基因mRNA表达方面的变化,探讨其联合作用的分子生物学机制。方法将NB细胞分为A组(对照组)、B组(9-cis RA用药组)、C组(γ-IFN用药组)和D组(9-cis RA和γ-IFN联合用药组)4组,在处理后5d收集各组细胞,用实时荧光定量逆转录聚合酶链反应法(fluorescent quantitative reverse transcription polymerase chain reaction,FQ-RT-PCR)检测细胞MYCN和MDR1基因mRNA的表达变化并对其进行相关性分析。结果 9-cis RA和γ-IFN体外皆可下调NB细胞MYCN和MDR1基因mRNA的表达,二者联合应用具有协同效应;两基因的表达呈显著的正相关关系。结论 9-cis RA协同?-IFN在体外诱导NB细胞分化、凋亡及生长抑制的作用机制可能为共同下调MYCN和MDR1基因mRNA的表达,一方面抑制了NB细胞原癌基因的生物学表现,另一方面预防了多药耐药(multidrug resistance,MDR),为其联合应用提供分子生物学依据和理论指导。Objective： To detect the variation of MYCN and MDR1 mRNA expression and investigate the molecular mechanisms of joint action when using 9-cis retinoic acid（RA） and gamma-interferon（γ-IFN） in combination to induce human neuroblastoma（NB） SK-N-SH cell line differentiation in vitro.Methods： The cells were divided into A（control group）,B（treated with 9-cis RA）,C（treated with γ-IFN） and D（treated with 9-cis RA and γ-IFN in combination） groups.The cells were collected at the 5th day after treatment.The expressions of MYCN and MDR1 mRNA were detected by fluorescent quantitative reverse transcription polymerase chain reaction（FQ-RT-PCR） and correlation analysis of these two genes was done.Results： Both of 9-cis RA and γ-IFN could down-regulate the expressions of MYCN and MDR1 mRNA of NB cells and had synergistic effect by combined therapy and the expression of these 2 genes showed marked positive correlation.Conclusion： The synergistic mechanism of a combination of 9-cis RA and γ-IFN on inducing differentiation,apoptosis and growth inhibition of human NB cells is the reduction of MYCN and MDR1 mRNA expressions through complementary action.On the one hand,it suppresses biology display of cellular proto-oncogene in NB,on the other hand,it prevents multidrug resistance（MDR）.These results also provide a molecular biology basis and rational guidance for establishing a combination therapeutic approach for clinical use.

关 键 词：神经母细胞瘤 9-顺式维甲酸 干扰素 细胞分化 MYCN MDR1 

分 类 号：R739.4[医药卫生—肿瘤]