Erythropoietin inhibits γ-irradiation-induced apoptosis by upregulation of Bcl-2 and decreasing the activation of caspase 3 in human UT-7/erythropoietin cell line

• Published in: Clinical and experimental pharmacology & physiology 2010-05, Vol.37 (5-6), p.624-629
• Main Authors: Liu, Yuan-Yuan, She, Zhen-Jue, Yao, Ming-Hui
• Format: Article
• Language: English
• Subjects: apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Bcl-2; Bcl-2/Bax ratio; Blotting, Western; caspase 3; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cell Survival - drug effects; Cell Survival - radiation effects; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; erythropoietin; Erythropoietin - pharmacology; Gamma Rays - adverse effects; Humans; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Recombinant Proteins; Up-Regulation; UT-7/EPO cell line; γ-irradiation
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/j.1440-1681.2010.05370.x

Summary 1. Erythropoietin (EPO) can reverse radiotherapy‐induced anaemia by stimulating bone marrow cells to produce erythrocytes. However, there are limited studies that address the mechanisms by which EPO exerts its beneficial effects in radiotherapy‐induced anaemia. In the present study, we used a human bone marrow‐derived EPO‐dependent leukaemia cell line UT‐7/EPO that progressed further in erythroid development to evaluate the anti‐apoptotic effects of EPO on irradiated human erythroid progenitor. 2. The UT‐7/EPO cells exposed to γ‐irradiation were cultured in the presence or absence of EPO at a concentration of 7 U/mL. The cell viability, cell apoptosis and the expression of apoptosis‐related proteins Bcl‐2, Bax and caspase 3 were examined. 3. The results showed that EPO protected the viability of human UT‐7/EPO cells exposed to γ‐irradiation. EPO significantly inhibited γ‐irradiation‐induced apoptosis in human UT‐7/EPO cells: a significant decrease in the percentage of apoptotic cells was observed (62, 69 and 62% at 24, 48 and 72 h, respectively). Furthermore, EPO significantly increased the expression of Bcl‐2 protein and the relative Bcl‐2/Bax ratio, and decreased the activation of caspase 3 and formation of the p17 and p12 cleavage in similar conditions. 4. In conclusion, EPO exerts anti‐apoptotic effects on irradiated human UT‐7/EPO cells through upregulation of Bcl‐2 protein and the relative Bcl‐2/Bax ratio, and by decreasing the activation of caspase 3. These findings may contribute to our understanding of the beneficial function of EPO in radiotherapy‐induced anaemia.