Abstract 13P
Background
Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In the DAPA-HF trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine,a nutraceutical, significantly reduces myocardial infarct size and the incidence of ventricular arrhythmia, improves cardiac function, ameliorates myocardial apoptosis.
Methods
Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3, methylglyoxal and leukotrienes-B4. Expression of pAMPK and IL-6 were performed through western blot.
Results
Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p<0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin. No significant changes in Leukotriene B4 expression were seen. IL-6 levels were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group).
Conclusions
Berberine and Dapagliflozin exerts significant cardioprotective effects in cardiac cells exposed to the HER2-bloking agent Trastuzumab. Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ricerca Corrente Project, Ministero della Salute.
Disclosure
All authors have declared no conflicts of interest.