title: Proteomic analysis of bladder cancer indicates Prx-I as a key molecule in BI-TK/GCV treatment system.
abstract: In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats. Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment. Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA). These findings yield new insights into the therapy of bladder cancer, revealing Prx-I as a new therapeutic target and indicating BI-TK/GCV system as a prospective therapy by down-regulation of Prx-I through NF-κB signaling pathway.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: YongYong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: HongQing
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Life Science, Chongqing Medical University, Chongqing, China.
authors.forename: MingJun
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001644:Bifidobacterium / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D016328:NF-kappa B / Q000378:metabolism; D054464:Peroxiredoxins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D054464:Peroxiredoxins; D013937:Thymidine Kinase; D015774:Ganciclovir