Proteomics Analysis of Trastuzumab Toxicity in the H9c2 Cardiomyoblast Cell Line and its Inhibition by Carvedilol

• Published in: Current pharmaceutical biotechnology Vol. 21; no. 13; p. 1377
• Main Authors: Beiranvand, Elham, Torkashvand, Fatemeh, Ostad, Seyed N, Mirzaie, Mehdi, Ardakani, Esmat M, Zandi, Fatemeh, Sardari, Soroush, Salekdeh, Ghasem H, Shokrgozar, Mohammad A, Vaziri, Behrouz
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2020
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Agents, Immunological - toxicity; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cardiomyopathies - prevention & control; Carvedilol - pharmacology; Carvedilol - therapeutic use; Cell Line; Cell Survival - drug effects; Computer Simulation; Down-Regulation; Female; Humans; Myoblasts, Cardiac - drug effects; Myoblasts, Cardiac - metabolism; Myoblasts, Cardiac - pathology; Proteome - metabolism; Proteomics; Receptor, ErbB-2 - metabolism; Trastuzumab - therapeutic use; Trastuzumab - toxicity; cardiomyoblast; trastuzumab; translation; Cardiotoxicity; proteomics; carvedilol
• ISSN: 1873-4316
• DOI: 10.2174/1389201021666200515135548

Heart dysfunctions are the major complications of trastuzumab in patients with Human Epidermal growth factor Receptor-2 (HER2)-positive breast cancers. In this study, the cytotoxicity of trastuzumab on H9c2 cardiomyoblasts was demonstrated, and the proteome changes of cells were investigated by a tandem mass tagging quantitative approach. The Differentially Abundant Proteins (DAPs) were identified and functionally enriched. We determined that carvedilol, a non-selective beta-blocker, could effectively inhibit trastuzumab toxicity when administrated in a proper dose and at the same time. The proteomics analysis of carvedilol co-treated cardiomyoblasts showed complete or partial reversion in expressional levels of trastuzumab-induced DAPs. Downregulation of proteins involved in the translation biological process is one of the most important changes induced by trastuzumab and reversed by carvedilol. These findings provide novel insights to develop new strategies for the cardiotoxicity of trastuzumab.