他莫昔芬（TAM）是一种有效治疗乳腺癌和卵巢癌的抗癌药物。然而，心脏毒性风险增加是与 TAM 相关的长期临床问题，而其潜在机制仍不清楚。在这里，我们在心肌细胞和荷瘤或非荷瘤小鼠中进行了实验，证明 TAM 通过负责活性氧的 IL-6/p-STAT3/PGC-1α/IL-6 反馈环路诱导心脏损伤物种（ROS）积累。与非荷瘤小鼠相比，荷瘤小鼠注射TAM后表现出更强的心脏毒性，但没有显着差异。体外实验表明STAT3磷酸化抑制剂可以增加PGC-1α的表达并通过减少ROS来保护心肌细胞。由于肿瘤具有较高的STAT3磷酸化和IL-6表达水平，我们的研究结果表明联合TAM和STAT3抑制剂可能是一种有效的治疗策略，可以提供肿瘤杀伤和心脏保护功能。需要进一步的体内研究来充分阐明TAM和STAT3抑制剂联合治疗的效果和机制。版权所有©2023。Elsevier B.V.出版。

Tamoxifen (TAM) is an effective anticancer drug for breast and ovarian cancer. However, increased risk of cardiotoxicity is a long-term clinical problem associated with TAM, while the underlying mechanisms remain unclear. Here, we performed experiments in cardiomyocytes and tumor-bearing or nontumor-bearing mice, and demonstrated that TAM induced cardiac injury via the IL-6/p-STAT3/PGC-1α/IL-6 feedback loop, which is responsible for reactive oxygen species (ROS) accumulation. Compared with non-tumor bearing mice, tumor-bearing mice showed stronger cardiac toxicity after TAM injection, although there was no significant difference. In vitro experiments demonstrated STAT3 phosphorylation inhibitor can increase PGC-1α expression and protect cardiomyocyte via decreasing ROS. Since tumor has higher STAT3 phosphorylation and IL-6 expression level, our research results indicated combining TAM and STAT3 inhibitor might be an effective treatment strategy which can provide both tumor killing and cardioprotective function. Further in vivo research is needed to fully elucidate the effect and mechanisms of the combination therapy of TAM and STAT3 inhibitor.Copyright © 2023. Published by Elsevier B.V.