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Ginsenoside Rg2 Attenuated Trastuzumab-Induced Cardiotoxicity in Rats
Guang Liu1,2, Jinli Zhang2, Fangyi Sun2
1Graduate School of Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050000, China.
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.
Insights
Ginsenoside Rg2 protects against Trastuzumab-induced cardiotoxicity in breast cancer patients. This study shows Rg2 reduces heart damage and cardiomyocyte apoptosis by downregulating proapoptotic proteins.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Trastuzumab (TZM) is a vital therapy for HER2-positive breast cancer.
- TZM treatment is associated with significant cardiotoxicity, limiting its clinical use.
- Ginsenoside Rg2 is a natural compound with demonstrated biological activities.
Purpose of the Study:
- To investigate the protective effects of Ginsenoside Rg2 against Trastuzumab-induced cardiotoxicity.
- To elucidate the underlying molecular mechanisms of Rg2's cardioprotective action.
Main Methods:
- A rat model of Trastuzumab-induced cardiotoxicity was established.
- Rats were pretreated with Ginsenoside Rg2 before TZM administration.
- Echocardiography, RNAseq, and cardiomyocyte assays (colony formation, flow cytometry, Western blot) were performed.
Main Results:
- Ginsenoside Rg2 attenuated Trastuzumab-induced left ventricular dysfunction in rats.
- Rg2 significantly reduced TZM-induced apoptosis in primary human cardiomyocytes.
- Rg2 downregulated the expression of proapoptotic proteins (caspase-3, caspase-9, BAX) in both rat hearts and cardiomyocytes.
Conclusions:
- Ginsenoside Rg2 effectively inhibits Trastuzumab-induced cardiotoxicity.
- The cardioprotective mechanism involves the downregulation of proapoptotic pathways.
- Ginsenoside Rg2 holds potential for preventing Trastuzumab-related heart damage in breast cancer patients.
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