高迁移率族蛋白A2在肿瘤发生和血管形成中的双重作用

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (9): 975-980.

高迁移率族蛋白A2在肿瘤发生和血管形成中的双重作用

吕颖慧^1,2, 龚玉华¹, 刁勇^1,2, 许瑞安^1,2, 王启钊^1,2

¹华侨大学分子药物学研究所,泉州 362021,福建;
²分子药物教育部工程研究中心,泉州 362021,福建

收稿日期:2011-08-03 修回日期:2011-08-30 出版日期:2011-09-26 发布日期:2011-10-11
通讯作者: 王启钊,男,博士,助理研究员,硕导,研究方向:基因治疗。Tel: 0595-22690838 E-mail: lyh4444@hqu.edu.cn
作者简介:吕颖慧,女,博士,助理研究员,硕导,研究方向:基因治疗。Tel: 0595-22690838 E-mail: longeryh@hqu.edu.cn
基金资助:
国家自然科学基金(30900822);福建省高校杰出青年人才培育计划(王启钊);华侨大学校基金(09BS517、基地专项)资助项目

HMGA2 play important roles both in tumorigenesis and angiogenesis

LV Ying-hui^1,2, GONG Yu-hua¹, DIAO Yong^1,2, XU Rui-an^1,2, WANG Qi-zhao^1,2

¹Institute of Molecular Medicine, Hua-qiao University, Quanzhou 362021, Fujian, China;
²Molecular Medicine Engineering Research Center, Ministry of Education, Quanzhou 362021, Fujian, China

Received:2011-08-03 Revised:2011-08-30 Online:2011-09-26 Published:2011-10-11

摘要/Abstract

摘要： 目的: 探讨高迁移率族蛋白A2(HMGA2)在肿瘤发生和血管形成中的作用。方法: 采用Clontech公司软件设计靶向人HMGA2基因的5条小干扰RNA(siRNA)序列,常规培养肿瘤细胞系和血管内皮细胞系,利用脂质体2000将HMGA2 siRNA导入细胞,通过MTT方法和Transwell模型检测细胞的增殖和迁移能力,采用小管形成实验检测血管内皮细胞的小管形成能力,荧光定量PCR方法检测细胞内的HMGA2 mRNA的变化。结果: 5条siRNA中,HMGA2 siRNA1、3、5不但能抑制肿瘤细胞的增殖,还可抑制血管内皮细胞的增殖、迁移和小管形成,尤其以HMGA2 siRNA5最为明显,处理组细胞的相对增长率分别为:Hela 63.2%±6.5%(P<0.01);人肺腺癌SPC-A1,86.8%±3.5%(P<0.01);人脐静脉内皮细胞(ECV-304),58.5%±6.3%(P<0.01);人膀胱上皮细胞株(HUVEC),60.3%±7.3%(P<0.01)。HMGA2 siRNA5抑制两种血管内皮细胞的迁移(P<0.01),并降低HMGA2基因的表达(P<0.01)。结论: HMGA2除了在肿瘤发生过程中起作用之外,在血管形成中同样具有重要作用。

关键词: 高迁移率族蛋白A2, 血管形成, 肿瘤发生, RNA干扰, 基因治疗

Abstract: AIM: To analyze the roles of high mobility group A2 protein (HMGA2) in tumorigenesis and angiogenesis. METHODS: 5 siRNAs targeting HMGA2 gene (HMGA2 siRNA1-5) were designed, synthesized, and transfected into cells using Lipofactamine 2000. MTT assay, transwell assay and tube formation assay were applied to evaluate the effects of these siRNAs on cancer cells (SPC-A1 and Hela) and endothelial cells (ECV-304 and HUVEC). RESULTS: HMGA2 siRNA1, 3 and 5 inhibited the growth of all the cell lines that were tested. Among these siRNAs, HMGA2 siRNA5 show the best inhibition effect. The relative growth ratios were 63.2%±6.5% (P<0.01), 86.8%±3.5% (P<0.01), 58.5%±6.3% (P<0.01), and 60.3%±7.3% (P<0.01) for Hela, SPC-A1, EVC-304 and HUEVC cells, respectively. Furthermore, interfering the expression of HMGA2 affected the growth, migration, and tube formation of endothelial cells (P<0.01). CONCLUSION: HMGA2 protein plays important roles both in tumorigenesis and angiogenesis.

Key words: HMGA2, Angiogenesis, Tumorigenesis, RNAi, Gene therapy

中图分类号:

R965.2

吕颖慧, 龚玉华, 刁勇, 许瑞安, 王启钊. 高迁移率族蛋白A2在肿瘤发生和血管形成中的双重作用[J]. 中国临床药理学与治疗学, 2011, 16(9): 975-980.

LV Ying-hui, GONG Yu-hua, DIAO Yong, XU Rui-an, WANG Qi-zhao. HMGA2 play important roles both in tumorigenesis and angiogenesis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(9): 975-980.

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