Erythropoietin reduces cisplatin-induced apoptosis in renal carcinoma cells via a PKC dependent pathway

Abstract

Anaemia which develops as a consequence of malignancies is often treated using recombinant human erythropoietin (rhEpo). Epo is now known as an anti-apoptotic factor for a wide range of cell types that express Epo receptors (EpoRs) and its co-use with cancer therapies can act detrimentally to diminish therapy-induced apoptosis. This had not been analyzed for renal cell carcinomas (RCCs). We examined the influence of rhEPO on the ability of cisplatin to induce apoptosis in RCCs. Two RCC cell lines (SN12K1 and ACHN) were compared with a non-RCC renal epithelial cell line (HK2). Cells were treated with 50μM cisplatin with and without 200IU/mL rhEpo and were compared for apoptosis, mitosis and protein expression of EpoR, nuclear factor-κB (NFκB), protein kinase C (PKC), Bcl-2, Bax and cyclin-D1. Experiments were repeated with PKC promotion (PMA, 20nM) or inhibition (H7, 10μM). rhEpo reduced cisplatin-induced apoptosis in RCCs (p