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標題: 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
作者: May, Eugenie Wong Soon
Lin, Szu-Ting
Lin, Chi-Chen
Chang, Jo-Fan
Hung, Eric
Lo, Yi-Wen
Lin, Li-Hsun
Hu, Ren-Yu
Feng, Chi-Lun
Lin, Dai-Ying
Wu, Shine-Bei
Lee, Wen-Chi
Lyu, Kevin W
Chou, Hsiu-Chuan
Chan, Hong-Lin
關鍵字: DIGE;Doxorubicin;Resistance;Reticulocalbin-1;Uterine cancer
Project: Pharmacological research : the official journal of the Italian Pharmacological Society, Volume 90, Page(s) 1-17.
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.
ISSN: 1096-1186
DOI: 10.1016/j.phrs.2014.08.007
Appears in Collections:生物醫學研究所

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