Shackebaei Dareuosh, Hesari Mahvash, Gorgani Sara, Vafaeipour Zeinab, Salaramoli Sanaz, Yarmohammadi Fatemeh
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Tissue Engineering Research Group (TERG), Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Cell Biochem Biophys. 2025 Mar;83(1):43-52. doi: 10.1007/s12013-024-01475-7. Epub 2024 Aug 5.
Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects.
多柔比星（DOX）是一种化疗药物，已知会引起心脏代谢变化，导致潜在的心脏毒性。这些变化影响多种细胞功能和途径，例如破坏雷帕霉素的机制性靶点（mTOR）信号通路。该研究旨在通过一项体内系统评价来研究DOX对mTOR通路的影响。于2023年9月11日检索了数据库。我们最终纳入了30项体内研究，这些研究检测了心脏组织样本中的mTOR表达。本研究表明，PI3K/AKT/mTOR、AMPK/mTOR、p53/mTOR信号传导、mTOR/TFEB通路、p38 MAPK/mTOR、sestrin/mTOR以及KLF15/eNOS/mTORC1信号通路在DOX诱导的心脏毒性发展中起关键作用。这些通路的抑制或失调可导致氧化应激增加、细胞凋亡以及对心脏的其他不良影响。靶向和调节mTOR通路的策略，如使用雷帕霉素等mTOR抑制剂，有可能增强DOX的抗癌效果，同时减轻其心脏毒性副作用。
