Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner
(2023) In Cellular Oncology 46(4). p.953-967- Abstract
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... (More)
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.
(Less)
- author
- Huang, Shan
; Zhang, Nai-Qi
LU
; Xu, Chun-Jie
; Huang, Wu-Qing
; Li, Dong-Xue
; Li, Jun
; Yao, Lin-Li
; Sundquist, Kristina
LU
; Sundquist, Jan
LU
; Jiang, Shu-Heng
; Xing, Xin
; Hu, Li-Peng
; Zhang, Zhi-Gang
; Ji, Jianguang
LU
and Zhang, Xue-Li
(Less) - organization
- publishing date
- 2023-03-20
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cellular Oncology
- volume
- 46
- issue
- 4
- pages
- 953 - 967
- publisher
- Springer
- external identifiers
-
- pmid:36939950
- scopus:85150471207
- ISSN
- 2211-3428
- DOI
- 10.1007/s13402-023-00789-7
- language
- English
- LU publication?
- yes
- id
- 6f02cc57-787a-46bc-a105-ff5c369bb85b
- date added to LUP
- 2023-03-23 19:53:35
- date last changed
- 2024-06-15 01:40:28
@article{6f02cc57-787a-46bc-a105-ff5c369bb85b,
abstract = {{<p>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.</p><p>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<br>
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.<br>
</p><p>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.</p><p>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.</p>}},
author = {{Huang, Shan and Zhang, Nai-Qi and Xu, Chun-Jie and Huang, Wu-Qing and Li, Dong-Xue and Li, Jun and Yao, Lin-Li and Sundquist, Kristina and Sundquist, Jan and Jiang, Shu-Heng and Xing, Xin and Hu, Li-Peng and Zhang, Zhi-Gang and Ji, Jianguang and Zhang, Xue-Li}},
issn = {{2211-3428}},
language = {{eng}},
month = {{03}},
number = {{4}},
pages = {{953--967}},
publisher = {{Springer}},
series = {{Cellular Oncology}},
title = {{Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner}},
url = {{http://dx.doi.org/10.1007/s13402-023-00789-7}},
doi = {{10.1007/s13402-023-00789-7}},
volume = {{46}},
year = {{2023}},
}