文章：

小豆蔻通过mTOR介导的自噬与顺铂协同抗人骨肉瘤细胞

Cardamom synergizes with cisplatin against human osteosarcoma cells by mTOR-mediated autophagy 

原文发布日期：2025-03-26

英文摘要：

Cisplatin (DDP), a frontline chemotherapeutic agent in osteosarcoma (OS) treatment, is frequently paired with other compounds to enhance its therapeutic potency. Cardamom (CAR), a natural flavonoid, exhibits significant inhibitory effects on human OS cells while minimizing toxic side effects. In this study, we combined CAR and DDP to treat OS, revealing that the DDP/CAR combination synergistically inhibits the growth of human OS cells in vitro and in vivo. Network pharmacological analysis indicated that mammalian target of rapamycin (mTOR) may be an important cross-target for DDP/CAR combination. Notably, this combined treatment significantly reduced mTOR phosphorylation and elevated autophagy levels within OS cells. At the mechanistic level, the DDP/CAR regimen enhanced apoptosis and compromised the viability of OS cells by triggering autophagy. This impact was attenuated by the use of the mTOR activator MHY and the autophagy inhibitor hydroxychloroquine (HCQ). Furthermore, in DDP-resistant cell lines, CAR was able to mitigate DDP resistance by bolstering autophagy levels. In general, our results suggest that CAR bolstering autophagy levels DDP against OS cells through the induction of mTOR-mediated autophagy. 

摘要翻译：

顺铂（DDP）作为骨肉瘤（OS）治疗的一线化疗药物，常与其他化合物联用以增强其治疗效力。豆蔻明（CAR）作为一种天然黄酮类化合物，在显著抑制人OS细胞的同时可减轻毒副作用。本研究联合使用CAR与DDP治疗OS，发现DDP/CAR组合在体外和体内均能协同抑制人OS细胞的生长。网络药理学分析表明，哺乳动物雷帕霉素靶蛋白（mTOR）可能是DDP/CAR组合的重要交叉靶点。值得注意的是，该联合治疗显著降低了OS细胞内mTOR磷酸化水平并提升了自噬水平。在机制层面，DDP/CAR方案通过触发自噬增强了OS细胞凋亡并削弱了细胞活力。使用mTOR激活剂MHY和自噬抑制剂羟氯喹（HCQ）可减弱这种效应。此外，在DDP耐药细胞系中，CAR能够通过增强自噬水平来缓解DDP耐药性。总体而言，我们的研究结果表明CAR通过诱导mTOR介导的自噬增强DDP对抗OS细胞的效应。

原文链接：

Cardamom synergizes with cisplatin against human osteosarcoma cells by mTOR-mediated autophagy