Li Sang-Lin, Ye Feng, Cai Wei-Jun, Hu Huai-Dong, Hu Peng, Ren Hong, Zhu Fu-Fan, Zhang Da-Zhi
Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education of China, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
J Cell Biochem. 2010 Mar 1;109(4):625-33. doi: 10.1002/jcb.22413.
In order to understand the molecular mechanisms of multidrug resistance (MDR) in ovarian cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the cisplatin-resistant COC1/DDP cell line and its parental COC1 cell line as a model. A total number of 28 proteins differentially expressed were identified, and then the differential expression levels of partially identified proteins were confirmed by Western blot analysis and/or real-time RT-PCR. Furthermore, the association of PKM2 and HSPD1, two differentially expressed proteins, with MDR were analyzed, and the results showed that they could contribute considerably to the cisplatin resistance in ovarian cancer cell. The differential expression proteins could be classified into eight categories based on their functions, that is, calcium binding proteins, chaperones, extracellular matrix, proteins involved in drug detoxification or repair of DNA damage, metabolic enzymes, transcription factor, proteins related to cellular structure and proteins relative to signal transduction. These data will be valuable for further study of the mechanisms of MDR in the ovarian cancer.
为了了解卵巢癌多药耐药（MDR）的分子机制，我们采用了等压标签相对和绝对定量（iTRAQ）的蛋白质组学方法，随后进行液相色谱-串联质谱（LC-MS/MS）分析，以顺铂耐药的COC1/DDP细胞系及其亲本COC1细胞系作为模型。共鉴定出28种差异表达的蛋白质，然后通过蛋白质印迹分析和/或实时逆转录聚合酶链反应（RT-PCR）对部分鉴定出的蛋白质的差异表达水平进行了验证。此外，分析了两种差异表达蛋白质PKM2和HSPD1与多药耐药的关系，结果表明它们对卵巢癌细胞的顺铂耐药有显著影响。差异表达的蛋白质根据其功能可分为八类，即钙结合蛋白、伴侣蛋白、细胞外基质、参与药物解毒或DNA损伤修复的蛋白质、代谢酶、转录因子、与细胞结构相关的蛋白质以及与信号转导相关的蛋白质。这些数据对于进一步研究卵巢癌多药耐药机制具有重要价值。
