Baicalin reduces sunitinib-induced cardiotoxicity in renal carcinoma PDX model by inhibiting myocardial injury, apoptosis and fibrosis
Background and purpose: Sunitinib, a multi-targeted tyrosine kinase inhibitor, has anticancer function but it’s clinical use is often limited by cardiovascular complications. Baicalin is a flavonoid extracted from radix scutellariae that has been demonstrated various pharmacological activities including anti-inflammatory property, but its potential effects in sunitinib -induced cardiotoxicity have not been clarified. In this study, we to investigate the effect of baicalin in sunitinib-induced cardiotoxicity in vivo by using patient-derived xenograft (PDX) model.
Material and Methods: Female Nod Scid mice with PDX were treated with vehicle, sunitinib (50 mg/kg/d), baicalin (100 mg/kg/d) or baicalin and sunitinib for 6 weeks. The tumor volume and weight of tumor-bearing mice were measured, and cardiovascular functions were evaluated by testing the Heart index and blood biochemical indicators, and by H&E, Masson and TUNEL staining.
Results: Sunitinib therapy and combination therapy effectively inhibited the growth of renal tumors. Combination therapy inhibited sunitinib-induced increase of creatine kinase (CK) and lactate dehydrogenase (LDH), and ameliorated the heart parameters. Moreover, baicalin effectively protected SU-induced cardiac dysfunction by decreased the injury, apoptosis, and fibrosis.
Conclusion: Collectively, our results demonstrate that baicalin as a potential cardioprotective approach for cardiovascular complications during sunitinib regimen.
