Referenced in: none

Automatically associated channels: Slo1

Title: Impact of Na+/Ca2+ Exchangers on Therapy Resistance of Ovary Carcinoma Cells.

Authors: Lisann Pelzl, Zohreh Hosseinzadeh, Kousi Alzoubi, Tamer Al-Maghout, Sebastian Schmidt, Christos Stournaras, Florian Lang

Journal, date & volume: Cell. Physiol. Biochem., 2015 , 37, 1857-68

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26584285

Abstract
According to previous observations, enhanced store-operated Ca2+-entry (SOCE) accomplished by the pore forming ion channel unit Orai1 and its regulator STIM1 contribute to therapy resistance of ovary carcinoma cells. Ca2+ signaling is further shaped by Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether therapy resistance is further paralleled by altered expression and/or function of Na+/Ca2+-exchangers.In therapy resistant (A2780cis) and therapy sensitive (A2780sens) ovary carcinoma cells transcript levels were estimated from RT-PCR, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/Ca2+-exchanger activity from the increase of [Ca2+]i (x0394;[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free extracellular perfusate by Na+ free and Ca2+ containing (2 mM) extracellular perfusate, as well as cell death from PI -staining in flow cytometry.The transcript levels of NCX3, NCKX4, NCKX5, and NCKX6, slope and peak of x0394;[Ca2+]i as well as Ica were significantly higher in therapy resistant than in therapy sensitive ovary carcinoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted x0394;[Ca2+]i and significantly augmented the cisplatin-induced cell death of therapy resistant ovary carcinoma cells without significantly modifying cisplatin-induced cell death of therapy sensitive ovary carcinoma cells.Enhanced Na+/Ca2+-exchanger activity may contribute to the therapy sensitivity of ovary carcinoma cells.