乳腺癌是全世界女性的主要癌症，阿霉素 (DOX) 等化疗药物有可能显着延长生存期，尽管代价是引起严重的心血管毒性。炎症已成为促进心血管毒性重塑的重要生物过程。血清糖皮质激素激酶 1 (SGK1) 在各种炎症性疾病中的作用已得到广泛研究。在这里，我们研究了 SGK1 在 DOX 诱导的 HL-1 心肌细胞系和荷瘤小鼠模型中的心脏毒性中功能的分子机制。 SGK1 在 DOX 诱导的心脏毒性模型中上调，并伴有炎症因子水平升高。此外，抑制SGK1可抑制心肌细胞内核因子κB（NFκB）的磷酸化，从而抑制炎症因子的产生和心肌细胞的凋亡，具有心脏保护作用。同时，靶向SGK1的小干扰RNA抑制乳腺癌细胞的增殖。相反，SGK1的过度表达会增加NFκB的磷酸化，加重心肌损伤。总之，我们的研究表明 SGK1 通过促进 NFκB 活性来促进 DOX 诱导的心脏炎症和细胞凋亡。我们的结果表明，抑制 SGK1 可能是一种有效的治疗策略，可以提供抗肿瘤和心脏保护功能。需要进一步的体内研究来充分阐明SGK1抑制剂和DOX联合治疗乳腺癌的效果和机制。版权所有©2023 Elsevier B.V.保留所有权利。

Breast cancer is the predominant cancer among women worldwide, and chemotherapeutic agents, such as doxorubicin (DOX), have the potential to significantly prolong survival, albeit at the cost of inducing severe cardiovascular toxicity. Inflammation has emerged as a crucial biological process contributing to the remodeling of cardiovascular toxicity. The role of serum glucocorticoid kinase 1 (SGK1) in various inflammatory diseases has been extensively investigated. Here, we studied the molecular mechanisms underlying the function of SGK1 in DOX-induced cardiotoxicity in HL-1 cardiomyocyte cell lines and in a tumor-bearing mouse model. SGK1 was upregulated in the DOX-induced cardiotoxicity model, accompanied by increased levels of inflammatory factors. Furthermore, inhibition of SGK1 suppresses the phosphorylation of nuclear factor-kappa B (NFκB) in cardiomyocytes, which inhibits the production of inflammatory factors and apoptosis of cardiomyocytes, and has cardioprotective effects. Simultaneously, small interfering RNA targeting SGK1 inhibited the proliferation of breast cancer cells. Conversely, overexpression of SGK1 increases the phosphorylation of NFκB and aggravates myocardial injury. In conclusion, our study demonstrates that SGK1 promotes DOX-induced cardiac inflammation and apoptosis by promoting NFκB activity. Our results indicate that inhibiting SGK1 might be an effective treatment strategy that can provide both tumor-killing and cardioprotective functions. Further in vivo research is needed to fully elucidate the effects and mechanisms of combination therapy with SGK1 inhibitors and DOX in breast cancer treatment.Copyright © 2023 Elsevier B.V. All rights reserved.