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