[1]李 敏,谌 茜,马 倬,等.eIF4E 在非小细胞肺癌耐药性中的作用[J].南京师大学报(自然科学版),2014,37(02):91.
　Li Min,Chen Xi,Ma Zhuo,et al.eIF4E Promotes Drug Resistance in Non-small Cell Lung Carcinoma[J].Journal of Nanjing Normal University(Natural Science Edition),2014,37(02):91.
点击复制

eIF4E 在非小细胞肺癌耐药性中的作用()
分享到：

《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

卷:
第37卷
期数:
2014年02期
页码:
91
栏目:
生命科学
出版日期:
2014-06-30

文章信息/Info

Title:
eIF4E Promotes Drug Resistance in Non-small Cell Lung Carcinoma
作者:
李 敏; 谌 茜; 马 倬; 吴丹丹; 倪 萍; 翟溯澜; 李 萍; 邹美娟; 王雪融
南京医科大学基础医学院药理学系,江苏南京210029
Author(s):
Li Min; Chen Xi; Ma Zhuo; Wu Dandan; Ni Ping; Zhai Sulan; Li Ping; Zou Meijuan; Wang Xuerong
Department of Pharmacology,School of Medicine,Nanjing Medical University,Nanjing 210029,China
关键词:
非小细胞肺癌; eIF4E; 厄洛替尼; 耐药性; EGFR
Keywords:
NSCLC; eIF4E; erlotinib; drug resistance; EGFR
分类号:
R965. 2;R734. 2
文献标志码:
A
摘要:
探讨eIF4E 对厄洛替尼耐药细胞株细胞增殖的影响及作用机制. 在配对的厄洛替尼敏感和耐药细胞株(HCC827-EP、HCC827-ER)上,采用实时定量PCR 检测mRNA 水平的变化,Western Blot 检测蛋白水平的变化;通过SRB 检测细胞的生长和药物的抑制率的变化. 以及用脂质体转染eIF4E 的小干扰RNA,用上述方法检测多种信号分子mRNA、蛋白水平的变化,及对细胞生长和对药物抑制率的影响. 结果显示,与HCC827-EP 相比,eIF4E在HCC827-ER 上高表达;HCC827
Abstract:
To observe the effects of eIF4E on the proliferation of erlotinib resistant cells and mechanism. Paired erlotinib sensitive and resistant HCC827-EP and HCC827-ER cells were used. Protein and mRNA expression levels were detected by Western blot and quantitative RT-PCR. The 5 ds growth curve and inhibition effects of erlotinib were determined by SRB assay. Downregulation of eIF4E expression were achieved by transfection of cells with siRNA targeting eIF4E using lipofectamine,and nonsense siRNA were used as control. eIF4E expression was increased in HCC827-ER cells compared with HCC827-EP cells. And downregulation of eIF4E expression inhibited the growth of HCC827-ER cells(P<0. 05)and sensitized their reponses erlotinib possibly through downregualtion of eIF4E expression( P <0. 05). Downregulation of eIF4E expression inhibited the growth of NSCLCs and enhanced the inhibitory effects of erlotinib.

参考文献/References:

[1]Jemal A,Siegel R,Ward E,et al. Cancer statistics,2008[J]. CA:A Cancer Journal for Clinicians,2008,58(2):71-96.
[2] Ferlay J,Shin H R,Bray F,et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[ J]. International Journal of Cancer,2010,127(12):2893-2917.
[3] Kosaka T,Yamaki E,Mogi A,et al. Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer[J/ OL]. BioMed Research International,2011:7[2011-04-11]. http:/ / dx. doi. org/10. 1155/2011/165214.
[4] Cappuzzo F,Ciuleanu T,Stelmakh L,et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer:a mul-ticentre,randomised,placebo-controlled phase 3 study[J]. The Lancet Oncology,2010,11(6):521-529.
[5] Goodfellow I G,Roberts L O. Eukaryotic initiation factor 4E[J]. The International Journal of Biochemistry and Cell Biology, 2008,40(12):2 675-2 680.
[6] De Benedetti A,Graff J R. eIF-4E expression and its role in malignancies and metastases[J]. Oncogene,2004,23(18):3 189-3 199.
[7] Graff J R,Konicek B W,Carter J H,et al. Targeting the eukaryotic translation initiation factor 4E for cancer therapy[ J]. Cancer Research,2008,68(3):631-634.
[8] Thumma S C,Kratzke R A. Translational control:a target for cancer therapy[J]. Cancer Letters,2007,258(1):1-8.
[9] Ma Z,Zhu L,Luo X,et al. Perifosine enhances mTORC1-targeted cancer therapy by activation of GSK3βin NSCLC cells[J].Cancer Biology and Therapy,2012,13(11):1 009-1 017.
[10] Mathis J M, Willians B J, Sibley D A, et al. Cancer-specific targeting of an adenovirus-delivered herpes simplex virus thymidine kinase suicide gene using translational control[J]. The Journal of Gene Medicine,2006,8(9):1 105-1 120.
[11] Nowak D E,Tian B,Jamaluddin M,et al. RelA Ser276 phosphorylation is required for activation of a subset of NF-κB-dependent genes by recruiting cyclin-dependent kinase 9/ cyclin T1 complexes[J]. Molecular and Cellular Biology,2008,28(11):3 623-3 638.
[12] Zhou B B S,Peyton M,He B,et al. Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer[J]. Cancer Cell,2006,10(1):39-50.
[13] Pao W,Miller V A,Politi K A,et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain[J]. PLoS Medicine,2005,2(3):e73.
[14] Chen G,Kronenberger P,Teugels E,et al. Effect of siRNAs targeting the EGFR T790M mutation in a non-small cell lung cancer cell line resistant to EGFR tyrosine kinase inhibitors and combination with various agents[ J]. Biochemical and Biophysical Research Communications,2013,431(3):623-629.
[15] Maheswaran S, Sequist L V, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells[ J]. New England Journal of Medicine,2008,359(4):366-377.
[16] Kobayashi S,Boggon T J,Dayaram T,et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib[J]. New England Journal of Medicine,2005,352(8):786-792.
[17] Rosenwald I B. The role of translation in neoplastic transformation from a pathologist爷s point of view[J]. Oncogene,2004,23 (18):3 230-3 247.
[18] Coqueret O. Linking cyclins to transcriptional control[J]. Gene,2002,299(1):35-55.
[19] Inaba T,Matsushime H,Valentine M,et al. Genomic organization,chromosomal localization,and independent expression of human cyclin D genes[J]. Genomics,1992,13(3):565-574.

相似文献/References:

[1]吴丹丹,倪 萍,孙 更,等.eIF4E在CXCL12诱导的胃癌转移中的作用和机制[J].南京师大学报(自然科学版),2015,38(02):93.
　Wu Dandan,Ni Ping,Sun Geng,et al.eIF4E Promotes CXCL12 Induced Metastasis of Gastric Cancer[J].Journal of Nanjing Normal University(Natural Science Edition),2015,38(02):93.

备注/Memo

备注/Memo:
收稿日期:2013-09-19.
基金项目:国家自然科学基金(30873099、81102458、811172004)、基础医学院优势学科、校引进人才启动基金.
通讯联系人:王雪融,博士,教授,研究方向:肿瘤药理. E-mail:wangxrwn@ hotmail.com
更新日期/Last Update: 2014-06-30