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

被引：1

作者：

Beiranvand, Elham ^{[1
]}

Torkashvand, Fatemeh ^{[1
]}

Ostad, Seyed N. ^{[2
]}

Mirzaie, Mehdi ^{[3
,4
]}

Ardakani, Esmat M. ^{[1
]}

Zandi, Fatemeh ^{[1
]}

Sardari, Soroush ^{[1
]}

Salekdeh, Ghasem H. ^{[5
]}

Shokrgozar, Mohammad A. ^{[6
]}

Vaziri, Behrouz ^{[1
]}

机构：

[1] Pasteur Inst Iran, Biotechnol Res Ctr, Prot Chem & Prote Lab, Tehran, Iran

[2] Univ Tehran Med Sci, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran

[3] Macquarie Univ, Dept Mol Sci, Sydney, NSW, Australia

[4] Macquarie Univ, Australian Proteome Anal Facil, Sydney, NSW, Australia

[5] ACECR, Cell Sci Res Ctr, Dept Mol Syst Biol, Royan Inst Stem Cell Biol & Technol, Tehran, Iran

[6] Pasteur Inst Iran, Natl Cell Bank Iran, Tehran, Iran

来源：

CURRENT PHARMACEUTICAL BIOTECHNOLOGY | 2020年 / 21卷 / 13期

关键词：

Cardiotoxicity; trastuzumab; proteomics; carvedilol; cardiomyoblast; translation; CARDIAC DYSFUNCTION; HEART-FAILURE; BETA-BLOCKERS; APOPTOSIS; CARDIOTOXICITY; CARDIOMYOPATHY; MITOCHONDRIAL; CHEMOTHERAPY; MODULATION; RELEASE;

D O I：

10.2174/1389201021666200515135548

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Objective: Heart dysfunctions are the major complications of trastuzumab in patients with Human Epidermal growth factor Receptor-2 (HER2)-positive breast cancers. Methods: 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. Results: 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. Conclusion: 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.

引用

页码：1377 / 1385

页数：9

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