The effect of EMD 87580, an Na+/H+ isoform 1 inhibitor, on the rate of cell proliferation in mouse lung adenocarcinoma cells

Abstract

BackgroundDysregulated pH is an emerging hallmark that maybe permissive for cancer progression. The Na+/H+ exchanger (NHE1) is one of the most notable pH regulating transporters and as such warrants further investigation for its role in non small cell lung cancer (NSCLC).MethodsNHE1 protein expression and the rate of cell proliferation were examined in cultured mouse lung adenocarcinoma cells ±10μM NHE1 inhibitor (EMD 87580) or Etoposide for 24 or 48 hours using western blotting and the MTT assay, respectively.ResultsWestern blotting demonstrated an increase in NHE1 protein expression in mouse lung adenocarcinoma cells. In the presence of EMD 87580 (N), NHE1 protein expression showed a trend towards reduction vs. control group (C) (100% C vs. 61.5% N). Treatment of mouse lung adenocarcinoma cells with EMD 87580 for 24 hours did not alter the rate of cell proliferation. Similarly, Etoposide, an anticancer topoisomerase inhibitor, had no effect on the rate of cell proliferation following 24 hours of treatment (92.8±6.3%). However, 48 hours of treatment with EMD 87580 revealed a trend towards reduction in the rate of cell proliferation in mouse lung adenocarcinoma cells (100±11.3% C vs. 77.4±2.6% N). The rate of cell proliferation was significantly less in mouse lung adenocarcinoma cells treated with Etoposide (34.9±7.3%).ConclusionTaken together, these data demonstrate that NHE1 protein was over expressed in the mouse lung adenocarcinoma cells. NHE1 inhibition regresses cell proliferation with prolonged treatment. It is evident the tumor progression and metastasis require NHE1.