Yang Yijin, Feng Zhenyu, Zhou Fengying, Sun Xuyang, Shang Jinshu, Zhang Ningning, Xia Yunlong, Xie Yunpeng
Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Dalian, People's Republic of China.
Phytother Res. 2025 Jul;39(7):3241-3253. doi: 10.1002/ptr.8525. Epub 2025 Jun 13.
Doxorubicin (DOX)-induced cardiotoxicity (DIC) by the chemotherapeutic drug seriously affects the prognosis of patients with cancer. Therefore, it is significant to actively explore the underlying mechanisms of DIC and develop safe and effective adjuvant therapies to improve DIC. As a traditional Chinese medicine monomer, BCA can treat cardiovascular diseases. However, whether BCA is able to inhibit DOX-induced myocardial injury without affecting its anticancer effect is unclear.
We divided tumor-bearing mice into four groups, constructed a heart failure model by administering DOX, and treated with BCA. Histopathological staining was performed (WGA, HE, IF, IHC, etc.), WB, qPCR, and serum detection of SOD and MDA. In vitro experiments, the effects of BCA and DOX in both kinds of cells were demonstrated by various experiments in primary cardiomyocytes and tumor cells panc02 of neonatal rats.
The results showed that BCA could inhibit DOX-induced abnormal cardiac function in mice, improve heart failure, and inhibit the expression of ANP and BNP. It inhibited the level of myocardial oxidative stress and reduced the number of myocardial vacuolation and the degree of myocardial fibrosis in mice. BCA reduced DOX-induced oxidative stress in NRCMs. In terms of tumors, BCA cooperates with DOX to inhibit the occurrence and development of panc02 and reduce the body weight of tumors. It inhibited the expression of PCNA and promoted the expression of BAX. In vitro experiments, BCA cooperated with DOX to inhibit the proliferation and metastasis of panc02.
To sum up, BCA can affect the occurrence and development of DOX-induced myocardial injury through multiple targets and pathways and does not interfere with the anti-tumor effect of DOX. This study seeks new drugs for DOX-induced myocardial injury and provides new ideas for the treatment of inhibiting DOX-induced myocardial injury and the research of related diseases.
化疗药物阿霉素（DOX）诱导的心脏毒性（DIC）严重影响癌症患者的预后。因此，积极探索DIC的潜在机制并开发安全有效的辅助治疗方法以改善DIC具有重要意义。作为一种中药单体，BCA可治疗心血管疾病。然而，BCA是否能够在不影响其抗癌效果的情况下抑制DOX诱导的心肌损伤尚不清楚。
我们将荷瘤小鼠分为四组，通过给予DOX构建心力衰竭模型，并给予BCA治疗。进行组织病理学染色（WGA、HE、IF、IHC等）、WB、qPCR以及血清SOD和MDA检测。在体外实验中，通过新生大鼠原代心肌细胞和肿瘤细胞panc02中的各种实验证明了BCA和DOX在两种细胞中的作用。
结果表明，BCA可抑制DOX诱导的小鼠心脏功能异常，改善心力衰竭，并抑制ANP和BNP的表达。它抑制心肌氧化应激水平，减少小鼠心肌空泡化数量和心肌纤维化程度。BCA降低了NRCMs中DOX诱导的氧化应激。在肿瘤方面，BCA与DOX协同抑制panc02的发生发展并减轻肿瘤体重。它抑制PCNA的表达并促进BAX的表达。在体外实验中，BCA与DOX协同抑制panc02的增殖和转移。
综上所述，BCA可通过多个靶点和途径影响DOX诱导的心肌损伤的发生发展，且不干扰DOX的抗肿瘤作用。本研究为DOX诱导的心肌损伤寻找新的药物，为抑制DOX诱导的心肌损伤的治疗及相关疾病的研究提供了新思路。
