Proteomic analysis to dissect mitoxantrone resistance-associated proteins in a squamous lung carcinoma

Anticancer Res. 2007 May-Jun;27(3A):1277-84.

Abstract

Background: Mitoxantrone resistance has been related to the expression of a drug efflux pump breast cancer resistance pump (BCRP) but little is known of the intracellular protein changes. In this work, differential protein expression in a squamous lung carcinoma cell line, DLKP, and its mitoxantrone-resistant variant (DLKP-Mitox) was investigated to elucidate other changes associated with mitoxantrone resistance.

Materials and methods: Differential protein expression between DLKP and DLKP-Mitox was investigated using 2D-DIGE technology. Proteins of interest were identified by MALDI-ToF mass spectrometry. Western blotting was used to confirm and validate some of these changes.

Results: Biological variation analysis in Decyder software revealed a total of 343 proteins to be differentially regulated with p < 0.05. Identification of 61 proteins of interest by mass spectrometry revealed changes in proteins involved in many cellular processes including apoptosis and differentiation.

Conclusion: Alterations in these cellular processes and proteins present alternative sites to circumvent resistance to mitoxantrone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / genetics
  • Acridines / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mitoxantrone / pharmacology*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Proteomics / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tetrahydroisoquinolines / pharmacology

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Acridines
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Tetrahydroisoquinolines
  • Mitoxantrone
  • Elacridar