Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Sanhueza, Carlos¹  Araos, Joaquin¹  Naranjo, Luciano¹  Toledo, Fernando^1,2  Beltran, Ana R.^3,4  Ramirez, Marco A.^1,4  Gutierrez, Jaime^1,5  Pardo, Fabian^1,6  Leiva, Andrea¹  Sobrevia, Luis^1,7,8 

[1] Pontificia Univ Catolica Chile, Fac Med, Sch Med, Div Obstet & Gynaecol,CMPL, Santiago 8330024, Chile

[2] Univ Bio Bio, Dept Basic Sci, Fac Sci, Chillan 3780000, Chile

[3] Univ Antofagasta, Dept Educ, Fac Educ, Antofagasta 1270300, Chile

[4] Univ Antofagasta, Biomed Dept, Fac Hlth Sci, Antofagasta 1270300, Chile

[5] Univ San Sebastian, Fac Hlth Sci, CSDRL, Santiago 7510157, Chile

[6] Univ Valparaiso, Metab Dis Res Lab, Ctr Res Dev & Innovat Hlth Aconcagua Valley, Sch Med,Fac Med, San Felipe Campus, San Felipe 2172972, Chile

[7] Univ Seville, Dept Physiol, Fac Pharm, E-41012 Seville, Spain

[8] Univ Queensland, Fac Med & Biomed Sci, UQCCR, Herston, Qld 4029, Australia

关键词: NHE1;    pHi;    Human;    Ovarian cancer;    Cell proliferation;   

DOI  :  10.1016/j.bbadis.2016.10.013

来源: Elsevier

【 摘 要 】

Cancer cells generate protons (H+) that are extruded to the extracellular medium mainly via the Na+/H+ exchanger 1 (NHE1), which regulates intracellular pH (pHi) and cell proliferation. In primary cultures of human ascites-derived ovarian cancer cells (haOC) we assayed whether NHE1 was required for pHi modulation and cell proliferation. Human ovary expresses NHE1, which is higher in haOC and A2780 (ovarian cancer cells) compared with HOSE cells (normal ovarian cells). Basal pHi and pHi recovery (following a NH4Cl pulse) was higher in haOC and A2780, compared with HOSE cells. Zoniporide (NHE1 inhibitor) caused intracellular acidification and pHi recovery was independent of intracellular buffer capacity, but reduced in NHE1 knockdown A2780 cells. Zoniporide reduced the maximal proliferation capacity, cell number, thymidine incorporation, and ki67 (marker of proliferation) fluorescence in haOC cells. SLC9A1 (for NHE1) amplification associated with lower overall patient survival. In conclusion, NHE1 is expressed in human ovarian cancer where it has a pro-proliferative role. Increased NHE1 expression and activity constitute an unfavourable prognostic factor in these patients. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

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