Identification of proteins associated to multi-drug resistance in LoVo human colon cancer cells

Michele Visentin, Maria Paola Simula, Franca Sartor, Alessandra Petrucco, Valli De Re, Giuseppe Toffoli

Research output: Contribution to journalArticle

Abstract

Multi-drug resistance (MDR) limits the effectiveness of chemotherapy. P-glycoprotein encoded by the MDR1 gene, is known to be implicated in MDR phenotype, but other factors could be determinant in MDR. The aim of this study was to investigate new molecular factors potentially associated with the MDR phenotype using a proteomic approach. Two dimensional fluorescence difference gel electrophoresis (2D-DIGE) and MALDI-TOF peptide mass fingerprinting were used to determine differentially expressed proteins between LoVo human colon carcinoma cell line and one of its MDR sublines (LoVo-R1). Thirty-four differentially expressed proteins were identified. They were classified into five groups based on their biological functions: i) proteins involved in energy request pathways, ii) in detoxification pathways, iii) in cell survival activity, iv) in drug transport and v) in chaperone functions. Among these proteins, endothelin 1 and proteasome subunit β2 regulations were validated by immunofluorescence and Western blotting, respectively, showing complete consistency with 2D-DIGE results. In conclusion, the proteomic approach indicates that multiple mechanisms are simultaneously involved in MDR. These might be useful in the search for new forms of interventional therapeutic approaches for MDR reversal.

Original languageEnglish
Pages (from-to)1281-1289
Number of pages9
JournalInternational Journal of Oncology
Volume34
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • Difference in gel electrophoresis
  • Mass spectrometry
  • Multi-drug resistance
  • P-glycoprotein
  • Proteomics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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