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Cardioprotective role of trans retinoic acid in trastuzumab-induced cardiotoxicity through modulation of Erk2 signalling pathway

 
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Research Article  
dx.doi.org/10.18081/2333-5106/015-10/631-643
American Journal of BioMedicine Volume 3, Issue 10, pages 631-643
Published: October 23, 2015


Jun Fana,b, Cheng Yanga,b, Dong-Qing China, Alexis Romanosa, Eva Wanga, Monica M. Vargasa, Hao Chenga mail of corresponding author

Abstract

Therapeutic treatment with trastuzumab (Trz) has demonstrated a significant reduction in morbidity and mortality in breast cancer patients, there is severe cardiac side effects that must be considered. Clinical studies have estimated that 5% to 10% of patients who receive trastuzumab in the adjuvant setting of breast cancer develop cardiac dysfunction. The precise mechanism underlying trastuzumab-induced cardiac dysfunction is unknown. Furthermore, the extracellular signal-regulated kinase (Erk) signaling pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, differentiation and motility. The objective of this study used trans retinoic acid to inhibit Erk2 activity, ATRA attenuated trastuzumab-induced activation of Erk2 pathway. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs) for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α), Western immunoblotting assay for Erk2, and used troponin I for cardiac injury marker. LV function was determined using a pressure-volume catheter (Millar Instruments, Houston, TX). Trastuzumab treated Erk2 KO male mice reduced post-myocardial inflammatory response, injury and improved cardiac function after preretreated with ATRA. These results suggest that ATRA could be a novel cardiotoxicity therapy following trastuzumab and further studies are required.

Keywords: Trastuzumab; Breast cancer; Cardiac dysfunction; Trans retinoic acid

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

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