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  • Huang, ShanShanghai Jiao Tong University (author)

Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023-03-20
  • Springer Science and Business Media LLC,2023

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:6f02cc57-787a-46bc-a105-ff5c369bb85b
  • https://lup.lub.lu.se/record/6f02cc57-787a-46bc-a105-ff5c369bb85bURI
  • https://doi.org/10.1007/s13402-023-00789-7DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • PURPOSE: 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.METHODS: 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 Apc min/+ 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. RESULTS: 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.CONCLUSIONS: 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Zhang, Nai-QiLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Region Skåne(Swepub:lu)na1267zh (author)
  • Xu, Chun-JieShanghai Jiao Tong University (author)
  • Huang, Wu-QingFujian Medical University (author)
  • Li, Dong-XueShanghai Jiao Tong University (author)
  • Li, JunShanghai Jiao Tong University (author)
  • Yao, Lin-LiShanghai Jiao Tong University (author)
  • Sundquist, KristinaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Icahn School of Medicine at Mount Sinai,Region Skåne(Swepub:lu)med-ksq (author)
  • Sundquist, JanLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Region Skåne,Icahn School of Medicine at Mount Sinai(Swepub:lu)med-jsu (author)
  • Jiang, Shu-HengShanghai Jiao Tong University (author)
  • Xing, XinShanghai Fengxian District Central Hospital (author)
  • Hu, Li-PengShanghai Jiao Tong University (author)
  • Zhang, Zhi-GangShanghai Jiao Tong University (author)
  • Ji, JianguangLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Region Skåne(Swepub:lu)med-jji (author)
  • Zhang, Xue-LiShanghai Jiao Tong University (author)
  • Shanghai Jiao Tong UniversityAllmänmedicin och klinisk epidemiologi (creator_code:org_t)

Related titles

  • In:Cellular Oncology: Springer Science and Business Media LLC46:4, s. 953-9672211-34282211-3436

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