Inhibition of Na+/H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility

被引：52
|
作者：
Yang, Xuekang [1 ]
Wang, Desheng [1 ]
Dong, Wei [1 ]
Song, Zhenshun [1 ]
Dou, Kefeng [1 ]
机构：
[1] Fourth Mil Med Univ, Dept Hepatobiliary Surg, Xijing Hosp, Xian 710032, Shannxi, Peoples R China
来源：
CANCER LETTERS | 2010年 / 295卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Hepatocellular carcinoma; Na+/H+ exchanger 1; Invasion; Migration; Tumor microenvironment; ACTIVATED PROTEIN-KINASE; ENDOTHELIAL GROWTH-FACTOR; SODIUM-PROTON EXCHANGER; MATRIX METALLOPROTEINASES; EXPRESSION; ERK; MICROENVIRONMENT; PATHWAYS; CELLS; OXYGEN;
D O I：
10.1016/j.canlet.2010.03.001
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Na+/H+. exchanger 1 (NHE1) plays a significant role in tumor metastasis. However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of NHE1 by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) is able to suppress migration and invasion of HepG2 cells under hypoxic conditions. In addition, hypoxia activated ERK1/2, which in turn promoted the production of MMP-2. MMP-9 and VEGF. EIPA's suppressive role was determined to act through down-regulation of MMP-2, MMP-9 and VEGF in an ERK1/2 dependent manner. The data demonstrate that NHE1 plays a role in HCC invasion and that NHE1 may be a potential therapeutic target for HCC treatment. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：198 / 204
页数：7
相关论文
共 30 条
  • [21] PHOTOLABELING OF TONOPLAST FROM SUGAR-BEET CELL-SUSPENSIONS BY [H-3] 5-(N-METHYL-N-ISOBUTYL)-AMILORIDE, AN INHIBITOR OF THE VACUOLAR NA+/H+ ANTIPORT
    BARKLA, BJ
    CHARUK, JHM
    CRAGOE, EJ
    BLUMWALD, E
    PLANT PHYSIOLOGY, 1990, 93 (03) : 924 - 930
  • [22] INHIBITION OF THE NA+/PROTON ANTIPORTER WITH THE AMILORIDE ANALOG 5-(N-METHYL-N-ISOBUTYL)AMILORIDE LEADS TO SUPERINDUCTION OF T-CELL PROLIFERATION INDUCED VIA THE ALTERNATE (CD2) PATHWAY
    KNAPP, W
    FISCHER, GF
    HOLTER, W
    CRAGOE, EJ
    MAJDIC, O
    MOLECULAR BASIS OF THE IMMUNE RESPONSE, 1988, 546 : 216 - 218
  • [23] Inhibition of the Na+/Proton antiporter with the amiloride analog 5-(N-methyl-N-isobutyl)amiloride leads to superinduction of T-cell proliferation induced via the alternate (CD2) pathway
    Knapp, Walter
    Fischer, Gottfried F.
    Holter, Wolfgang
    Cragoe, Edward J. Jr.
    Majdic, Otto
    Annals of the New York Academy of Sciences, 1988, 546
  • [24] INHIBITION OF THE NA+/PROTON ANTIPORTER WITH THE AMILORIDE ANALOG 5-(N-METHYL-N-ISOBUTYL)AMILORIDE LEADS TO SUPERINDUCTION OF T-CELL PROLIFERATION INDUCED VIA THE ALTERNATE (CD2) PATHWAY
    KNAPP, W
    FISCHER, GF
    HOLTER, W
    CRAGOE, EJ
    MAJDIC, O
    ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1988, 546 : 216 - 218
  • [25] 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside reduces glucose uptake via the inhibition of Na+/H+ exchanger 1 in isolated rat ventricular cardiomyocytes
    Segalen, Coralie
    Longnus, Sarah L.
    Baetz, Delphine
    Counillon, Laurent
    Van Obberghen, Emmanuel
    ENDOCRINOLOGY, 2008, 149 (04) : 1490 - 1498
  • [26] 5-(N,N-DIMETHYL)AMILORIDE INHIBITS ANGIOTENSIN-II-INDUCED HYPERTROPHY OF VASCULAR SMOOTH-MUSCLE CELLS - ROLE OF NA+/H+ EXCHANGE, CYTOSOLIC CA2+, AND EARLY GROWTH-RESPONSE GENES
    SACHINIDIS, A
    SCHULTE, KB
    SEUL, C
    KO, Y
    DUSING, R
    VETTER, H
    HYPERTENSION, 1994, 24 (03) : 394 - 394
  • [27] KR-32570, a novel Na+/H+ exchanger-1 inhibitor, attenuates hypoxia-induced cell death through inhibition of intracellular Ca2+ overload and mitochondrial death. pathway in H9c2 cells
    Kim, MJ
    Moon, CH
    Kim, MY
    Lee, S
    Yi, KY
    Yoo, SE
    Lee, SH
    Baik, EJ
    Jung, YS
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2005, 525 (1-3) : 1 - 7
  • [28] [Pt(O,O′-acac)(γ-acac)(DMS)] Alters SH-SY5Y Cell Migration and Invasion by the Inhibition of Na+/H+ Exchanger Isoform 1 Occurring through a PKC-ε/ERK/mTOR Pathway
    Muscella, Antonella
    Vetrugno, Carla
    Calabriso, Nadia
    Cossa, Luca Giulio
    De Pascali, Sandra Angelica
    Fanizzi, Francesco Paolo
    Marsigliante, Santo
    PLOS ONE, 2014, 9 (11):
  • [29] Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling
    Cheng, Shan
    Li, Yang
    Yang, Ying
    Feng, Duiping
    Yang, Longyan
    Ma, Qian
    Zheng, Shuai
    Meng, Ran
    Wang, Shuhui
    Wang, Songlin
    Jiang, Wen G.
    He, Junqi
    FEBS LETTERS, 2013, 587 (20) : 3289 - 3295
  • [30] [Pt(O,O'-acac)(γ-acac)(DMS)] Alters SH-SY5Y Cell Migration and Invasion by the Inhibition of Na+/H+ Exchanger Isoform 1 Occurring through a PKC-ε/ERK/mTOR Pathway (vol 9, e112186, 2014)
    Muscella, A.
    Vetrugno, C.
    Calabriso, N.
    Cossa, L. G.
    De Pascali, S. A.
    Fanizzi, F. P.
    PLOS ONE, 2015, 10 (03):
123