title: Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method.
abstract: Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance.
authors.affiliation: aDepartment of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital bDepartment of Gynecology and Obstetrics, Second West China Hospital cDepartment of Nursing, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xingchen
authors.initials: X
authors.lastname: Peng
authors.forename: Fengming M
authors.initials: FM
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Ren
authors.forename: Ping
authors.initials: P
authors.lastname: Ai
authors.forename: ShaoYong
authors.initials: S
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: XiaoLin
authors.initials: X
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D010751:Phosphopyruvate Hydratase