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.