Identification of DJ-1 as a contributor to multidrug resistance in human small-cell lung cancer using proteomic analysis

Proteomic approaches have been proven to provide an important tool in identifying drug resistance‐associated proteins. The aim of this study was to investigate the protein profiling of drug resistance‐related proteins in small‐cell lung cancer (SCLC) by proteomic analysis. The proteomic profiling was performed by two‐dimensional fluorescence difference gel electrophoresis (2D‐DIGE) coupled with MALDI‐TOF‐TOF of SCLC in the multidrug‐resistant cell line H69AR and its parental cell line H69. A total of 11 proteins were identified to be >2‐fold up‐or downregulated between the two cell lines. DJ‐1, one of the differently expressed proteins identified by proteomics, was further examined by immunohistochemistry staining in 116 cases of SCLC tissues. Immunohistochemical results demonstrated that DJ‐1 was expressed in 51.7% (60/116) of SCLC. DJ‐1 expression was correlated significantly with survival time of SCLC patients (P 0.05). Downregulation of DJ‐1 using DJ‐1‐siRNA in H69AR cells sensitized cancer cells to chemotherapeutic drugs through increasing drug‐induced cell apoptosis accompanied with G0‐G1 phase arrest. These findings suggest DJ‐1 may serve as a potential biomarker for chemoresistance and prognostic factor for patients with SCLC.