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Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis
Authors:Koh  Masahiro  Takahashi  Tsuyoshi  Kurokawa  Yukinori  Kobayashi  Teruyuki  Saito  Takuro  Ishida  Tomo  Serada  Satoshi  Fujimoto  Minoru  Naka  Tetsuji  Wada  Noriko  Yamashita  Kotaro  Tanaka  Koji  Miyazaki  Yasuhiro  Makino  Tomoki  Nakajima  Kiyokazu  Yamasaki  Makoto  Eguchi  Hidetoshi  Doki  Yuichiro
Affiliation:1.Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
;2.Center for Intractable Disease, Kochi University, Nankoku, Japan
;3.Department of Surgery, Ikeda City Hospital, Ikeda, Japan
;
Abstract: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.

Keywords:
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