Zoledronic acid effects the cell cycle signalling AURKA gene in MDA MB231 breast cancer cells

Abstract

Purpose: The drug Zoledronic acid (ZOL) has been extensively studied as a therapeutic strategy to treat breast cancers. Previous data show the triple negative breast (TNBC) samples are particularly sensitive to killing following exposure to the drug. The goal of this current study was to examine the effect of ZOL on TNBC and identify genes that might contribute to this sensitivity.Methods: A cell line model was used to perform experiments to determine the dose effect of ZOL on TNBC and the genes differentially expressed following drug exposure. Following treatment, the mode of death was established and the transcriptomes of the cells were examined via microarray and differentially expressed genes were identified and validated via transcript and protein expression analyses.Results: Data show that TNBC cells are sensitive to killing following ZOL, with cell death occurring via the autophagy mechanism. Data also show an enrichment in dysregulation in signalling events related to cell cycle regulation. Previous studies have shown involvement of the cell cycle regulator CDKN1A/p21. We observed similar involvement of CDKN1A/p21, but in addition we found down-regulation of the mitotic serine/threonine kinase AURKA gene. Conclusion:In autophagy associated cell death in TNBC, ZOL functions via cell cycle-mediated signalling events related to regulation of CDKN1A proteinase inhibitor and down-regulation of AURKA kinase.