In a mouse model of myocardial infarction-induced left ventricular dysfunction, empagliflozin reduced primary breast tumor growth, while carvedilol reduced metastatic clusters, with both treatments restoring MI-suppressed IFN-γ expression.
Do heart failure treatments (enalapril, carvedilol, or empagliflozin) attenuate tumor growth and metastasis in a mouse model of post-MI left ventricular dysfunction?
Specific heart failure treatments (empagliflozin and carvedilol) mitigate breast cancer growth and metastasis in a mouse model of MI-induced LV dysfunction, likely through restoration of immune signaling rather than direct anti-tumor effects.
BACKGROUND: Recent studies have shown that heart failure (HF) and left ventricular (LV) dysfunction are associated with enhanced tumor growth. However, whether treating LV dysfunction mitigates its impact on cancer progression remains unknown. We hypothesized that HF treatments would attenuate tumor growth in a rodent model of post-myocardial infarction (MI)-induced LV dysfunction, and that different pharmacological agents (carvedilol, enalapril, and empagliflozin) might exert distinct effects on tumor progression. METHODS: 4T1 metastatic breast cancer cells were injected, with a three-week follow-up. The effects of HF treatments on cancer progression were assessed by analyzing: (i) tumor size in vivo over 22 days, (ii) lung metastasis development and (iii) gene expression levels in tumor tissue by RNA sequencing. RESULTS: Enalapril reversed several MI-induced transcriptomic changes in tumor tissue. Empagliflozin reduced primary tumor growth, while carvedilol reduced metastatic clusters. These effects were absent in control mice without MI, and neither drug directly affected cultured 4T1 cells. Transcriptomic analysis revealed treatment-specific inflammatory pathway regulation. Notably, carvedilol and empagliflozin restored MI-suppressed IFN-γ expression in tumors, accompanied by increased STAT1 expression in 4T1 cells. CONCLUSION: Specific HF treatments can mitigate cancer growth in a mouse model of MI-induced LV dysfunction, with outcomes varying by treatment. These benefits occurred only with LV dysfunction, suggesting they result from changes in HF pathophysiology rather than direct drug effects on tumor cells. Restoration of immune signaling may contribute to these effects.
Civati et al. (Thu,) conducted a other in Myocardial infarction-induced left ventricular dysfunction and metastatic breast cancer (n=77). Enalapril, carvedilol, or empagliflozin vs. Vehicle was evaluated on Primary tumor growth, lung metastasis development, and gene expression levels. In a mouse model of myocardial infarction-induced left ventricular dysfunction, empagliflozin reduced primary breast tumor growth, while carvedilol reduced metastatic clusters, with both treatments restoring MI-suppressed IFN-γ expression.