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

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 beta2 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.

journal_name

Int J Oncol

authors

Visentin M,Simula MP,Sartor F,Petrucco A,De Re V,Toffoli G

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

1281-9

issue

5

eissn

1019-6439

issn

1791-2423

journal_volume

34

pub_type

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