Abstract
Aim Trastuzumab (TZM) is a monoclonal antibody drug for HER2-positive breast cancer by targeting epidermal growth factor 2, but it has significant cardiotoxicity. Ginsenoside Rg2 has shown a variety of biological activities. This study was aimed at investigating whether Rg2 attenuates TZM-induced cardiotoxicity. Methods A model of TZM-induced cardiotoxicity was established in Wistar rats, and the rats were pretreated with Rg2. After echocardiography analysis, the rats were killed and the hearts were dissected for RNAseq analysis. Primary human cardiomyocytes (HCMs) were treated with TZM with or without pretreatment with Rg2 and then subjected to a colony formation assay, flow cytometry analysis, and Western blot analysis for the detection of caspase-3, caspase-9, and BAX. Results TZM induced LV dysfunction in rats, but Rg2 could attenuate TZM-induced LV dysfunction. The mRNA levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated rats. The colony formation ability of HCMs was significantly lower in TZM-treated cells but was recovered after pretreatment with Rg2. The apoptosis rate of HCMs was significantly higher in TZM-treated cells but was significantly lower after pretreatment with Rg2. Moreover, protein levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated cells but were significantly lower after pretreatment with Rg2. Conclusion Ginsenoside Rg2 inhibited TZM-induced cardiotoxicity, and the mechanism may be related to the downregulation of the expression of proapoptotic proteins caspase-3, caspase-9, and BAX and the inhibition of TZM-induced apoptosis in cardiomyocytes. Ginsenoside Rg2 has a potential to be applied in patients with breast cancer to prevent TZM-induced cardiotoxicity.
Highlights
Trastuzumab (TZM) is a humanized monoclonal antibody used as a drug to target the extracellular domain of human epidermal growth factor receptor 2 (HER2) and has shown good therapy efficacy on the majority of patients with HER2-positive breast cancer [1]
The results showed that left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and left ventricular end-diastolic pressure (LVEDP) were significantly higher while IVSTd, IVSTs, LVPWd, LVPWs, ejection fraction (EF), fractional shortening (FS), and left ventricular systolic pressure (LVSP) were significantly lower in the T group than in the control group
We found that TZM induced LV dysfunction in rats, indicating the successful establishment of the model of TZM-induced cardiotoxicity
Summary
Trastuzumab (TZM) is a humanized monoclonal antibody used as a drug to target the extracellular domain of human epidermal growth factor receptor 2 (HER2) and has shown good therapy efficacy on the majority of patients with HER2-positive breast cancer [1]. Recent efforts have been focused on the development of antibody-drug conjugates of TZM with high affinity, specificity, and efficacy for the treatment of HER2-positive breast cancer [ 2, 3]. It is urgent to limit the cardiotoxicity of TZM to achieve maximum efficacy on breast cancer therapy. Ginsenoside Rg2 is one of the main compounds of ginseng that exert drug efficacy [7]. We wondered whether ginsenoside Rg2 could reduce TZM-induced cardiotoxicity.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
