Journal
PHARMACOLOGICAL RESEARCH
Volume 90, Issue -, Pages 1-17Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2014.08.007
Keywords
Reticulocalbin-1; DIGE; Doxorubicin; Resistance; Uterine cancer
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Funding
- NSC grant from National Science Council, Taiwan [100-2311-B-007-005, 101-2311-B-007-011, 102-2627-B-007-002, 102-2311-B-007-009]
- National Tsing Hua University [101N2725E1, 101N2771E1, 101N2051E1, 102N2048E1, 102N2759E1]
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Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2 mu M cells and MES-SA/DxR-8 mu M cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubian-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer. (C) 2014 Elsevier Ltd. All rights reserved.
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