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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References

1. American Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013.

2. Zhang X, Szeto C, Gao E, et al. Cardiotoxic and cardioprotective features of chronic β-adrenergic signaling. Circ Res 2013; 112(3):498-509. [PubMed]

3. Gutierrez C, Schiff R. HER2: Biology, detection, and clinical implications. Arch Pathol Lab Med 2011; 135:55–62. [PubMed]

4. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344:783–792. [PubMed]

5. Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK-PI3K/Akt pathway. Cell Biol Int 2014; 38(1):85-91. [PubMed]

6. Zhang H, Zhang JJ, Mei YW, et al. Trastuzumab-induced cardiac dysfunction: A ‘dual-hit’. Chin Med J 2011; 124(17):2764–2766. [PubMed]

7. Anderson WF, Katki HA, Rosenberg PS. Incidence of breast cancer in the United States: current and future trends. J Natl Cancer Inst 2011;18:1397–402. 

8. Santen RJ, Song RX, McPherson R, et al. The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol 2002; 80:239-256. [PubMed]

9. Dahabreh IJ, Linardou H, Siannis F, et al. Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist 2008;13:620–30. [PubMed]

10. Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 2005; 23:7820–6. [PubMed]

11. Gordon LI, Burke MA, Singh AT, et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J Biol Chem 2009; 284:2080–7. [PubMed]

12. Edvardsen T. Can modern echocardiographic techniques predict drug-induced cardiotoxicity? J Am Coll Cardiol 2011; 57(22):2271-2. [Abstract/Full-Text]

13. SMartín M, Esteva FJ, Alba E, et al. Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist 2009; 14(1):1-11. [Abstract/Full-Text]

14. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010; 28(1):92-8. [PubMed]

15. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354:809–820. [PubMed]

16. Liberato NL, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2007; 25:625–633. [PubMed]

17. Garrison LP, Jr, Lubeck D, Lalla D, et al. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer 2007; 110:489–498. [PubMed]

18. Lidgren M, Wilking N, Jonsson B, et al. Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer. Acta Oncol 2008; 47:1018–1028. [PubMed]

19. Zhao P, Ma W, Hu Z, Zang L, Tian Z, Zhang K, et al. Filamin A (FLNA) modulates chemosensitivity to docetaxel in triple-negative breast cancerthrough the MAPK/ERK pathway. J Neurosci 2012; 32(9):3235–3244. [PubMed]

20. ZKohno M, Pouyssegur J. Targeting the ERK signaling pathway in cancer therapy. Ann Med 2006; 38(3):200-11. [PubMed]

21. Wang X, Tournier C. Regulation of cellular functions by the ERK5 signalling pathway. Cell Signal 2006; 18:753-760. [PubMed]

22. Krishna M, Narang H. The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci 2008; 65:3525-3544. [PubMed]

23. Perez EA, Rodeheffer R. Clinical cardiac tolerability of trastuzumab. J Clin Oncol 2004; 22:322. [PubMed]

24. Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer 2002; 95:1592. [PubMed]

25. Yousif NG, Al-Amran FG. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovasc Disord 2011;11:62. [PubMed]

26. Musolino A, Naldi N, Bortesi B. et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26:1789–1796. [PubMed]

27. Bedard PL, Piccart-Gebhart MJ. Current paradigms for the use of HER2-targeted therapy in early-stage breast cancer. Clin Breast Cancer 2008; 8(suppl 4):S157–165. [PubMed]

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