A secretomic study on human hepatocellular carcinoma multiple drug-resistant cell lines.

The aim of this study was to identify pivotal dysregulated proteins that are biomarkers for multiple drug resistance (MDR) of human hepatocellular carcinoma (HCC). The secretome profiles of the human HCC MDR cell line BEL7402/5-FU and its parental cell line BEL7402 were comparatively analyzed using isobaric tags for the relative and absolute quantification (iTRAQ)-coupled 2D LC-MS/MS. In total, 279 differentially expressed proteins were identified, of which, with a consistent result in the duplex test, 131 proteins were overexpressed in BEL7402/5-FU compared to its parental cell line, and 56 proteins were underexpressed. Several differentially expressed proteins determined by western blot analysis were also validated. The association of MDR with one of the highly regulated proteins, α-2-HS-glycoprotein (AHSG) was determined. This study detailed the application of iTRAQ technology to MDR biomarkers in the HCC cell secretome. The results showed that differentially expressed proteins that may be associated with MDR of HCC provide valuable additional information with regard to understanding the role of MDR.