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Updated: Jun 27, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Comparative Analysis of Doxorubicin-Induced Cardiotoxicity in Tumor-Bearing and Non-Tumor-Bearing Mouse Models: A
Aonan Yu1,2, Rong Yang1,2, Yaojiang Wang1,2
1Department of Pharmacy, Bengbu Medical University, Bengbu 233030, China.
None:
Doxorubicin (DOX) is a widely used anthracycline chemotherapeutic agent whose clinical application is limited by cardiotoxicity. In clinical settings, chemotherapy is given to tumor-bearing patients, whereas most preclinical studies of DOX-related cardiotoxicity use non-tumor-bearing animal models, potentially missing context-dependent differences. To address this, we compared DOX-induced cardiotoxicity between non-tumor-bearing and tumor-bearing mouse models. Cardiac function was assessed by echocardiography, and serum biomarkers, histopathological changes, and cardiac transcriptomic profiles were analyzed. Tumor burden exacerbated DOX-induced increases in BNP and CK-MB levels and myocardial structural damage, whereas systolic function was significantly reduced in non-tumor-bearing mice but did not further decline in tumor-bearing mice. Transcriptomic analysis revealed that DOX treatment induced 2528 and 398 differentially expressed genes (DEGs) in non-tumor-bearing and tumor-bearing mice, respectively, compared with their respective controls. A total of 206 shared DEGs were identified, most of which showed consistent directions of change under both conditions, while 16 genes exhibited opposite expression patterns. Common DEGs were mainly enriched in immune-inflammatory responses, cell adhesion, and extracellular matrix (ECM)-receptor interaction pathways. In non-tumor-bearing conditions, DOX-specific mechanisms were mainly associated with ECM remodeling, oxidative stress, metabolic dysregulation, and p53-mediated apoptosis. In contrast, tumor-bearing conditions showed predominant enrichment of immune-related pathways, including JAK-STAT, Toll-like receptor, NOD-like receptor, and chemokine signaling. These findings suggest that tumor burden may modulate the molecular mechanisms of DOX-induced cardiotoxicity, revealing context-dependent differences and offering insights for future cardioprotective strategies.
