胰岛素受体底物1低表达促进头颈部鳞状细胞癌的侵袭转移

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (7): 744-749.

胰岛素受体底物1低表达促进头颈部鳞状细胞癌的侵袭转移

罗璇¹, 黄文斌², 翟溯澜¹, 马倬¹, 李萍¹, 王雪融¹

¹南京医科大学基础医学院药理学系,南京 210029,江苏;
²南京医科大学附属南京医院(南京市第一医院)病理科,南京 210006,江苏

收稿日期:2012-02-28 修回日期:2012-06-12 发布日期:2012-07-17
通讯作者: 王雪融,女,博士,教授,研究方向:肿瘤药理。Tel: 13813385723 E-mail: wangxrnj@gmail.com
作者简介:罗璇,女,硕士研究生,研究方向:肿瘤药理。Tel:15951890703 E-mail: luoxuan777@163.com

The role of downregulation of insulin receptor substrate 1 in the invasion and metastasis of head and neck squamous cell carcinoma

LUO Xuan¹, HUANG Wen-bin², ZHAI Su-lan¹, MA Zhuo¹, LI Ping¹, WANG Xue-rong¹

¹Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
²Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China

Received:2012-02-28 Revised:2012-06-12 Published:2012-07-17

摘要/Abstract

摘要： 目的: 研究胰岛素受体底物1(insulin receptor substrate 1, IRS-1)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)侵袭转移中的作用及其可能的机制。 方法: 应用定量RT-PCR法检测HNSCC患者淋巴结转移灶和原发灶癌组织中IRS-1 mRNA的表达,以及不同转移能力头颈部肿瘤细胞株上IRS-1 mRNA的表达。用Taqman探针法检测miR-9及U6的相对表达量。利用小干扰RNA技术阻抑IRS-1表达,肿瘤细胞侵袭实验检测IRS-1干扰前后对细胞侵袭能力的影响。用定量RT-PCR和Western blot检测上皮-间叶转化(epithelial-mesenchymal transition, EMT)的标志物E-cadherin及vimentin mRNA和蛋白的表达;用SRB法检测细胞存活率。 结果: (1)HNSCC患者淋巴结转移灶中IRS-1 mRNA的表达低于原发灶(P<0.05);高转移性HNSCC细胞株中IRS-1 mRNA的表达低于低转移性细胞株(P<0.05)。(2)下调IRS-1表达,肿瘤细胞的侵袭能力增强,上皮-间叶转化标志物E-cadherin表达下降,同时伴有miR-9表达的升高。 结论: IRS-1低表达可能通过上皮-间叶转化和上调miR-9而增强细胞的侵袭能力,促进HNSCC的转移。

关键词: 胰岛素受体底物1, 头颈部鳞状细胞癌, 转移, E-钙黏蛋白, miR-9

Abstract: AIM: To explore the role of insulin receptor substrate 1 (IRS-1) in the invasion and metastasis of head and neck squamous cell carcinoma(HNSCC) and potential mechanism. METHODS: IRS-1 mRNA expression in the metastatic lymph node and corresponding primary tumour tissues of HNSCC patients, in highly and poorly metastatic HNSCC cells were detec-ted byqRT-PCR. miR-9 and U6 expression were measured by the TaqMan microRNA qPCR. IRS-1 expression was downregulated by using siRNA. The effect of IRS-1 on cell invasive potency was examined by transwell invasion assay after IRS-1 interference. E-cadherin and vimentin were detected by qRT-PCR and Western blot. Cell survival rate was examined by SRB assay. RESULTS: IRS-1 mRNA expression decreased in the metastatic lymph node tumor tissues compared to primary tumor tissues of HNSCC patients(P<0.05). As well, its expression levels were lower in highly metastatic HNSCC cells compared to its parental poorly metastatic cells(P<0.05). IRS-1 knockdown promoted invasion of poorly metastatic 686LN cells and induced EMT in parallel with upregulation of miR-9 expression. CONCLUSION: Downregulation of IRS-1 may promote invasion and metastasis of head and neck squamous cell carcinoma by epithelial-mesenchymal transition and upregulating miR-9 expression.

Key words: Insulin receptor substrate 1 (IRS-1), Head and neck squamous cell carcinoma (HNSCC), Metastasis, E-cadherin, miR-9

中图分类号:

罗璇, 黄文斌, 翟溯澜, 马倬, 李萍, 王雪融. 胰岛素受体底物1低表达促进头颈部鳞状细胞癌的侵袭转移[J]. 中国临床药理学与治疗学, 2012, 17(7): 744-749.

LUO Xuan, HUANG Wen-bin, ZHAI Su-lan, MA Zhuo, LI Ping, WANG Xue-rong. The role of downregulation of insulin receptor substrate 1 in the invasion and metastasis of head and neck squamous cell carcinoma[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(7): 744-749.

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