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Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.

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.
AuthorsEugenie 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
JournalPharmacological research (Pharmacol Res) Vol. 90 Pg. 1-17 (Dec 2014) ISSN: 1096-1186 [Electronic] Netherlands
PMID25242635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • Calcium-Binding Proteins
  • Proteome
  • RCN1 protein, human
  • RNA, Small Interfering
  • Doxorubicin
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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