Proteomic Analysis to Dissect Mitoxantrone Resistance-associated Proteins in a Squamous Lung Carcinoma

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.