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

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

  • Biochim Biophys Acta Mol Basis Dis. 2017 Jan;1863(1):81-91. doi: 10.1016/j.bbadis.2016.10.013.
Carlos Sanhueza 1,  Joaquín Araos 2,  Luciano Naranjo 2,  Fernando Toledo 3,  Ana R Beltrán 4,  Marco A Ramírez 5,  Jaime Gutiérrez 6,  Fabián Pardo 7,  Andrea Leiva 2,  Luis Sobrevia 8
Affiliations

Affiliations

  • 1 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile. Electronic address: [email protected].
  • 2 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
  • 3 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán 3780000, Chile.
  • 4 Department of Education, Faculty of Education, Universidad de Antofagasta, Antofagasta 1270300, Chile; Biomedical Department, Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta 1270300, Chile.
  • 5 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Biomedical Department, Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta 1270300, Chile.
  • 6 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Cellular Signalling Differentiation and Regeneration Laboratory (CSDRL), Health Sciences Faculty, Universidad San Sebastian, Santiago 7510157, Chile.
  • 7 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Metabolic Diseases Research Laboratory, Center of Research, Development and Innovation in Health - Aconcagua Valley, San Felipe Campus, School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile.
  • 8 Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Queensland, Australia. Electronic address: [email protected].
PMID: 27773735 DOI: 10.1016/j.bbadis.2016.10.013
Abstract

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.

Keywords

Cell proliferation; Human; NHE1; Ovarian cancer; pHi.

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