可用证据表明，二吡咯酮增强阿司匹林的抗血栓作用，预防二次中风。阿司匹林是一种著名的非甾体抗炎药。该抗炎性特性已将阿司匹林转化成了潜在的用于炎症相关癌症，如结直肠癌（CRC）的药物。因此，我们旨在探讨二吡咯酮联合阿司匹林对 CRC 抗癌效果是否能得到改善。基于人群数据的临床分析评估了联合使用二吡咯酮和阿司匹林治疗 CRC 的疗效，与单一药物治疗相比，其抑制 CRC 效果。此疗效在不同的 CRC 小鼠模型，如正位异种移植小鼠模型、AOM/DSS小鼠模型、Apcmin /+ 小鼠模型和来自患者的异种移植（PDX）小鼠模型中被进一步验证。使用 CCK8 和流式细胞术测试药物对 CRC 细胞的体外作用。RNA-Seq、Western blotting、qRT-PCR 和流式细胞术被用于鉴定潜在分子机制。我们发现，二吡咯酮联合阿司匹林对 CRC 的抑制作用优于单药治疗。联合使用二吡咯酮和阿司匹林的增强抗癌效果依赖于产生的超载内质网（ER）应激和随后的促凋亡未折叠蛋白反应（UPR），这与其抗血小板作用不同。我们的数据表明，联合使用二吡咯酮和阿司匹林可以增强阿司匹林对 CRC 的抗癌效果。如果进一步的临床研究证实了我们的发现，这些发现可能被再利用作为辅助剂。© 2023. Springer Nature Switzerland AG.

Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole.Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apcmin/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms.We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect.Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.© 2023. Springer Nature Switzerland AG.