Abstract |
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-2μM cells and MES-SA/DxR-8μM 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 doxorubicin-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.
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Authors | Eugenie Wong Soon May, Szu-Ting Lin, Chi-Chen Lin, Jo-Fan Chang, Eric Hung, Yi-Wen Lo, Li-Hsun Lin, Ren-Yu Hu, Chi-Lun Feng, Dai-Ying Lin, Shine-Bei Wu, Wen-Chi Lee, Kevin W Lyu, Hsiu-Chuan Chou, Hong-Lin Chan |
Journal | Pharmacological research
(Pharmacol Res)
Vol. 90
Pg. 1-17
(Dec 2014)
ISSN: 1096-1186 [Electronic] Netherlands |
PMID | 25242635
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antibiotics, Antineoplastic
- Calcium-Binding Proteins
- Proteome
- RCN1 protein, human
- RNA, Small Interfering
- Doxorubicin
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Topics |
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
(drug effects)
- Calcium-Binding Proteins
(genetics, metabolism)
- Cell Line, Tumor
- Down-Regulation
(drug effects)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
(physiology)
- Electrophoresis, Gel, Two-Dimensional
- Female
- Humans
- Proteome
- RNA, Small Interfering
(administration & dosage)
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Up-Regulation
(drug effects)
- Uterine Neoplasms
(metabolism)
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