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

被引:22
作者
Li, Jun [1 ,2 ,3 ]
Vesey, David A. [1 ,2 ,4 ]
Johnson, David W. [1 ,2 ,4 ]
Gobe, Glenda [1 ,2 ]
机构
[1] Univ Queensland, Sch Med, Discipline Mol & Cellular Pathol, Brisbane, Qld 4006, Australia
[2] Univ Queensland, Sch Med, Ctr Kidney Dis Res UQ PAH, Brisbane, Qld 4006, Australia
[3] China Med Univ, Affiliated Hosp 1, Dept Urol, Shenyang, Peoples R China
[4] Princess Alexandra Hosp, Dept Renal Med, Brisbane, Qld 4102, Australia
关键词
apoptosis; renal cell carcinoma; PKC; erythropoietin; metastasis;
D O I
10.4161/cbt.6.12.4975
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (SN1 2K1 and ACHN) were compared with a non-RCC renal epithelial cell line (HK2). Cells were treated with 50 mu M cisplatin with and without 200 IU/mL rhEpo and were compared for apoptosis, mitosis and protein expression of EpoR, nuclear factor-kappa B (NF kappa B), protein kinase C (PKC), Bcl-2, Box and cyclin-D1. Experiments were repeated with PKC promotion (PMA, 20 nM) or inhibition (H7, 10 mu M). rhEpo reduced cisplatin-induced apoptosis in RCCs (p < 0.01), compared with HK-2s. EpoR expression was increased only in SN1 2K1 with rhEpo, with and without cisplatin. NF kappa B, Bax and Bcl-2 expression was unchanged. PKC protein expression was significantly reduced in cisplatin-treated RCCs with rhEpo, correlating with reduced apoptosis. When the PKC pathway was inhibited in these cells, levels of apoptosis returned to normal for cisplatin treatment, indicating activation of the PKC pathway by rhEpo. PMA promotion increased mitosis only in the RCCs, with and without rhEpo (p < 0.05). In summary, rhEPO reduced cisplatin-induced apoptosis of RCCs and promoted their mitosis via PKC-dependent pathways. This information indicates caution for use of rhEpo in RCC patients for anemias.
引用
收藏
页码:1944 / 1950
页数:7
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