Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis
© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association - 24(2021), 5 vom: 29. Sept., Seite 1037-1049 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Koh, Masahiro [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.01.2022 Date Revised 13.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10120-021-01184-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323385893 |
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| 100 | 1 | |a Koh, Masahiro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis |
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| 500 | |a Date Completed 13.01.2022 | ||
| 500 | |a Date Revised 13.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Gastric cancer | |
| 650 | 4 | |a Propranolol | |
| 650 | 4 | |a Repurposing drug | |
| 650 | 4 | |a β-Adrenergic receptor | |
| 650 | 4 | |a β-Blocker | |
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| 700 | 1 | |a Kurokawa, Yukinori |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Teruyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Saito, Takuro |e verfasserin |4 aut | |
| 700 | 1 | |a Ishida, Tomo |e verfasserin |4 aut | |
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| 700 | 1 | |a Yamashita, Kotaro |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Miyazaki, Yasuhiro |e verfasserin |4 aut | |
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| 700 | 1 | |a Eguchi, Hidetoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Doki, Yuichiro |e verfasserin |4 aut | |
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