Abstract
Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.
Highlights
Adriamycin (ADR) is a broad-spectrum anthracycline antibiotic derived from Streptomyces peucetius
Enzyme-linked immunosorbent assay (ELISA) kits for B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase-3 were purchased from Boster Biological Technology Co., Ltd. (Wuhan, China)
BW levels in two Pilose antler polypeptide (PAP)-3.2KD groups (100 and 200 mg/kg) groups were significantly increased at 12 days after PAP-3.2KD administration, compared to those in the ADR group (P < 0.05 and
Summary
Adriamycin (ADR) is a broad-spectrum anthracycline antibiotic derived from Streptomyces peucetius. ADR was used to treat acute leukemia, various malignant tumors, and other diseases [1]. At therapeutic doses, it could cause a series of severe toxic reactions, including bone marrow suppression, nausea, vomiting, nephrotoxicity and cardiac toxicity [2]. It could cause a series of severe toxic reactions, including bone marrow suppression, nausea, vomiting, nephrotoxicity and cardiac toxicity [2] Since ADR toxicity in the heart of patients with cancer is observed while ADR is used to treat cancer, the protective roles and mechanisms of PAP against ADR-induced myocardial injury are investigated
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