Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis.
Gastric cancer
Propranolol
Repurposing drug
β-Adrenergic receptor
β-Blocker
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
14
11
2020
accepted:
11
03
2021
pubmed:
31
3
2021
medline:
14
1
2022
entrez:
30
3
2021
Statut:
ppublish
Résumé
Despite improvements in gastric cancer treatment, the mortality associated with advanced gastric cancer is still high. The activation of β-adrenergic receptors by stress has been shown to accelerate the progression of several cancers. Accordingly, increasing evidence suggests that the blockade of β-adrenergic signaling can inhibit tumor growth. However, the effect of β-blockers, which target several signaling pathways, on gastric cancer remains to be elucidated. This study aimed to investigate the anti-tumor effects of propranolol, a non-selective β-blocker, on gastric cancer. We explored the effect of propranolol on the MKN45 and NUGC3 gastric cancer cell lines. Its efficacy and the mechanism by which it exerts anti-tumor effects were examined using several assays (e.g., cell proliferation, cell cycle, apoptosis, and wound healing) and a xenograft mouse model. We found that propranolol inhibited tumor growth and induced G1-phase cell cycle arrest and apoptosis in both cell lines. Propranolol also decreased the expression of phosphorylated CREB-ATF and MEK-ERK pathways; suppressed the expression of matrix metalloproteinase-2, 9 and vascular endothelial growth factor; and inhibited gastric cancer cell migration. In the xenograft mouse model, propranolol treatment significantly inhibited tumor growth, and immunohistochemistry revealed that propranolol led to the suppression of proliferation and induction of apoptosis. Propranolol inhibits the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis. These findings indicate that propranolol might have an opportunity as a new drug for gastric cancer.
Sections du résumé
BACKGROUND
Despite improvements in gastric cancer treatment, the mortality associated with advanced gastric cancer is still high. The activation of β-adrenergic receptors by stress has been shown to accelerate the progression of several cancers. Accordingly, increasing evidence suggests that the blockade of β-adrenergic signaling can inhibit tumor growth. However, the effect of β-blockers, which target several signaling pathways, on gastric cancer remains to be elucidated. This study aimed to investigate the anti-tumor effects of propranolol, a non-selective β-blocker, on gastric cancer.
METHODS
We explored the effect of propranolol on the MKN45 and NUGC3 gastric cancer cell lines. Its efficacy and the mechanism by which it exerts anti-tumor effects were examined using several assays (e.g., cell proliferation, cell cycle, apoptosis, and wound healing) and a xenograft mouse model.
RESULTS
We found that propranolol inhibited tumor growth and induced G1-phase cell cycle arrest and apoptosis in both cell lines. Propranolol also decreased the expression of phosphorylated CREB-ATF and MEK-ERK pathways; suppressed the expression of matrix metalloproteinase-2, 9 and vascular endothelial growth factor; and inhibited gastric cancer cell migration. In the xenograft mouse model, propranolol treatment significantly inhibited tumor growth, and immunohistochemistry revealed that propranolol led to the suppression of proliferation and induction of apoptosis.
CONCLUSIONS
Propranolol inhibits the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis. These findings indicate that propranolol might have an opportunity as a new drug for gastric cancer.
Identifiants
pubmed: 33782804
doi: 10.1007/s10120-021-01184-7
pii: 10.1007/s10120-021-01184-7
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Propranolol
9Y8NXQ24VQ
Matrix Metalloproteinase 2
EC 3.4.24.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1037-1049Informations de copyright
© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
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