LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Integr Cancer Ther. 2023 Jan-Dec;22:15347354231164621. doi: 10.1177/15347354231164621.
Doxorubicin (Dox) is a first-line chemotherapeutic agent applied in cancer treatment. Its long-term anticancer efficacy is restricted mainly due to its subsequent cardiotoxicity for patients. (PG), an important traditional Chinese herb, has been reported to eliminate phlegm, relieve cough, and reduce inflammatory diseases. Previous clinical studies found that PG has cardioprotective effects for early breast cancer patients who received Dox-based chemotherapy. However, the cellular and molecular mechanisms underlying PG-mediated cardiotoxic rescue remain elusive. This study aimed to explore the protective role and potential molecular mechanisms of PG on Dox-induced cardiac dysfunction in a mouse model of breast cancer. PG significantly alleviated myocardial damage and prevented cardiomyocyte apoptosis induced by Dox. The expression levels of cytochrome C and cleaved caspase-3 significantly decreased, and the levels of Bcl-XL and B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein increased following PG treatment. Furthermore, PG remarkably enhanced the antimetastatic efficacy (versus the Dox group) by regulating the balance of matrix metalloproteinases/tissue inhibitors of metalloproteinases.
多柔比星(Dox)是一种用于癌症治疗的一线化疗药物。其长期的抗癌疗效主要受到其对患者随后产生的心脏毒性的限制。(PG)是一种重要的传统中药,已被报道具有化痰、止咳和减轻炎症性疾病的作用。先前的临床研究发现,PG 对接受基于多柔比星的化疗的早期乳腺癌患者具有心脏保护作用。然而,PG 介导的心脏毒性挽救的细胞和分子机制仍不清楚。本研究旨在探讨 PG 在乳腺癌小鼠模型中对多柔比星诱导的心脏功能障碍的保护作用及其潜在的分子机制。PG 显著减轻了多柔比星引起的心肌损伤并预防了心肌细胞凋亡。PG 处理后,细胞色素 C 和裂解的半胱天冬酶-3 的表达水平显著降低,B 细胞淋巴瘤-2/ Bcl-2 相关 X 蛋白(Bcl-2)/Bcl-2 相关 X 蛋白的水平升高。此外,PG 通过调节基质金属蛋白酶/组织金属蛋白酶抑制剂的平衡显著增强了抗转移作用(与多柔比星组相比)。