Articulo
NHE1 MODULATES INTRACELLULAR PH AND CELL PROLIFERATION IN HUMAN OVARIAN CANCER
PLACENTA
Registro en:
1150344
1150344
Autor
Araos, Joaquin
Naranjo, L
Sanhueza, C
Leiva-Mendoza, Andrea Alejandra
Sobrevia, Luis
Institución
Resumen
Ovarian cancer is a gynaecological disease with high mortality rate. Cancer cells produce large amounts of protons (H+). The Na+/H+ exchanger 1 (NHE1) is one of the main H+ transport systems and participates in intracellular pH (pHi) control and cell proliferation, but its role in human ovarian cancer has not been described yet. Objectives: Our aim was to determine whether NHE1 plays a role in the pHi and proliferation in human ovarian cancer cells. Methods: NHE1 and Ki67 (proliferation marker) expression was assessed in ovarian non-tumour cell line (HOSE), tumour cell line (A2780), primary cultures of human ascites cancer cells (haOC), and in serial sections of ovary biopsies obtained from Hospital Clínico UC-CHRISTUS at the Pontificia Universidad Católica de Chile (Santiago de Chile). NHE1 activity in the absence or presence of zoniporide (100 nmol/L, 6 minutes, NHE1 inhibitor) was estimated by measuring pHi recovery rate (dpHi/dt) by the acid-pulse technique using 2,7-bicarboxyethyl-5,6-carboxyfluorescein (BCECF-AM) probe in a fluorimeter. Cell proliferation was evaluated by [H3]-thymidine incorporation. Results: NHE1 is the main contributor to dpHi/dt in HOSE (66 ± 11% of total dpHi/dt) and A2780 (98 ± 2% of total dpHi/dt) cell lines, and haOC (76 ± 8% of total dpHi/dt). Zoniporide reduced [H3]-thymidine incorporation in HOSE, A2780 and haOC cells. NHE1 was positively correlated with Ki67 in human ovarian tumour. Conclusion: These findings suggest that NHE1 plays a pro-proliferative role and regulates intracellular pHi in human ovarian cancer cells. Funding: FONDECYT 1150377/1150344 (Chile). Regular 2015 FONDECYT FONDECYT