Proteomic-based analysis for identification of proteins involved in 5-fluorouracil resistance in hepatocellular carcinoma

Curr Pharm Des. 2014;20(1):81-7. doi: 10.2174/138161282001140113125143.

Abstract

Background: Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance.

Methods: We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resistance in HCC. The differentially expressed proteins were validated by Western blot analysis.

Results: We identified 102 unique proteins including p16, maspin, PRDX6, PSMB7, MYL6, PHB, and HSP27 with alteration in SMMC- 7721/5-FU. Furthermore, down-regulation of PRDX6 and PSMB7 enhanced SMMC-7721/5-FU cells to 5-FU sensitivity.

Conclusions: Our study suggests that targeting drug resistant genes such as PRDX6 and PSMB7 could be a novel approach to overcome 5-FU resistance in HCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • DNA Primers
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Fluorouracil / therapeutic use*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Neoplasm Proteins / metabolism*
  • Prohibitins
  • Proteomics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antimetabolites, Antineoplastic
  • DNA Primers
  • Neoplasm Proteins
  • PHB protein, human
  • Prohibitins
  • Fluorouracil