Redox-proteomic analysis of doxorubicin resistance-induced altered thiol activity in uterine carcinoma

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• 作者：Szu-Ting Lin^a ; ¹ ; Yi-Wen Lo^b ; ¹ ; Shing-Jyh Chang^c ; ^d ; Wen-Ching Wang^e ; Margaret Dah-Tsyr Chang^e ; Ping-Chiang Lyu^a ; Yi-Wen Chen^a ; Hsiu-Chuan Chou^b ; ^{chouhc@mail.nhcue.edu.tw} ; Hong-Lin Chan^a ; ^{hlchan@life.nthu.edu.tw}
• 关键词：2D-DIGE ; two-dimensional differential gel electrophoresis ; CCB ; colloidal coomassie blue ; ICy dyes ; iodoacetyl cyanine dyes ; MALDI-TOF MS ; matrix assisted laser desorption ionization-time of flight mass spectrometry ; mPR ; membrane-associated progesterone
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2013
• 出版时间：5 May, 2013
• 年：2013
• 卷：78-79
• 期：Complete
• 页码：1-8
• 全文大小：908 K

文摘

Doxorubicin is an anticancer drug used in a wide range of cancer therapies; however, doxorubicin-induced drug resistance is one of the most serious obstacles of cancer chemotherapy. Recent studies have indicated that reduced oxidative stress levels in cancer cells induce drug resistance. However, the redox-modifications of resistance - associated cellular targets are largely unknown. Thus, the current study employed cysteine-labeling based two-dimensional differential gel electrophoresis (2D-DIGE) combined with MALDI-TOF mass spectrometry (MALDI-TOF MS) to analyze the effect of doxorubicin resistance on redox regulation in uterine cancer and showed 33 spots that were significantly changed in thiol reactivity. These proteins involve cytoskeleton regulation, signal transduction, redox-regulation, glycolysis, and cell-cycle regulation. The current work shows that the redox 2D-DIGE-based proteomic strategy provides a rapid method to study the molecular mechanisms of doxorubicin-induced drug resistance in uterine cancer. The identified targets may be used to further evaluate their roles in drug-resistance formation and for possible diagnostic or therapeutic applications.