The influence of erythropoietin on growth and survival in non-small cell lung cancer cell lines

2015 
Introduction: Lung cancer patients have the highest incidence of anaemia among patients with solid tumours. The use of recombinant human erythropoietin (rHuEpo) has consistently been shown to reduce the need of blood transfusions and increase the haemoglobin level in lung cancer patients with chemotherapy-induced anaemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor (EpoR) on tumour cells may be responsible for adverse events and eventually death. The question has been raised whether Epo promotes tumour growth and inhibits cell death of cancer cells. Objectives: This study investigated the presence and functionality of EpoR as well as the implications of Epo upon growth and survival in lung cancer cells. Methods: By using quantitative real time PCR, Western blot, and immunocytochemical staining, three non-small cell lung cancer (NSCLC) cell lines (A427, A549, NCI-H358) were analysed for EpoR and its specific downstream signalling pathways (JAK2-STAT5, PI3K-AKT, MAP kinase). We assessed the influence of 100 U/ml Epo on proliferation under ambient and hypoxic conditions (1% O 2 ) and cisplatin-induced apoptosis via caspase-3 under ambient conditions. Results: All NSCLC cell lines expressed EpoR mRNA and protein while levels differed considerably between cell lines. We found constitutive phosphorylation of EpoR and most of its downstream signalling pathways (STAT5, AKT, ERK1/2) independently of Epo administration. Epo did not promote tumour growth or protect from caspase-3 driven apoptosis. Conclusion: This study does not suggest any direct tumour promoting effects of Epo in NSCLC cells.
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