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.