靶向Hmga2基因的siRNA药物筛选及抗肿瘤作用  

Selection and anti-cancer effects of siRNAs targeting Hmga2 gene

作　　者：王启钊[1,2] 龚玉华[1] 吕颖慧[1,2] 费凌娜[1] 刘会杰[1] 刁勇[1,2] 许瑞安[1,2] 

机构地区：[1]华侨大学分子药物学研究所,福建泉州362021 [2]华侨大学分子药物教育部工程研究中心,福建泉州362021

出　　处：《药学学报》2011年第12期1444-1450,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30900822);教育部科学研究重点项目(210252);华侨大学校基金(09BS517;基地专项)

摘　　要：HMGA2是一种结构性转录因子,在肺癌等多种肿瘤中过表达,是肿瘤治疗的候选靶点之一。RNAi技术作为一种经济、有效的基因沉默工具,是肿瘤治疗的新手段。本文以Hmga2基因为靶点,设计并合成了5条siRNA(HMGA2 siRNA1-5),通过MTT、平板克隆、Transwell、流式细胞术等手段,研究其对肺癌细胞(NCI-H446和A549)增殖、克隆形成、迁移和凋亡等能力的影响。结果表明,HMGA2 siRNA1、3、5对肺癌细胞的各项性能具有不同程度的影响,其中HMGA2 siRNA5尤为明显。HMGA2 siRNA5主要通过沉默Hmga2基因影响细胞性能,与其干扰素效应关系不大。本文筛选获得了可有效沉默Hmga2基因的siRNA,其在体外具有良好的抗肺癌活性,是具有一定潜力的肿瘤基因治疗候选药物。High mobility group A2 protein（HMGA2）,an architectural factor,is highly expressed in various cancer types including lung cancers.It is a candidate target for cancer therapy.RNAi is an effective gene silencing method with low cost and less time-consuming.It is possible to exploit this technology in therapy.Here,5 siRNAs targeting Hmga2 gene（HMGA2 siRNA1-5） were designed and synthesized.MTT assay,colony formation assay,transwell assay and flow cytometry were used to evaluate the effects of these siRNAs on lung cancer cell lines（NCI-H446 and A549）.Results from cell proliferation,clone formation,migration and apoptosis showed that HMGA2 siRNA1,3,5 could affect these aspects for both lung cancer cell lines.Among the five siRNAs,HMGA2 siRNA5 showed the greatest inhibition effects.The inhibition effects of HMGA2 siRNA5 are sequence specific and are not due to the induction of interferon response.Taken together,siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene therapy.

关 键 词：RNAI HMGA2 SIRNA 肺癌 基因治疗 

分 类 号：R963[医药卫生—微生物与生化药学]