The β-adrenoceptor antagonist, propranolol, induces human gastric cancer cell apoptosis and cell cycle arrest via inhibiting nuclear factor κB signaling

• Published in: Oncology reports Vol. 24; no. 6; pp. 1669 - 1676
• Main Authors: Liao, Xinhua, Che, Xiangming, Zhao, Wei, Zhang, Danjie, Bi, Tieqiang, Wang, Guanghui
• Format: Journal Article
• Language: English
• Published: Greece 01-12-2010
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Cell Cycle - drug effects; Cell Cycle - genetics; Cell Line, Tumor; Cell Proliferation - drug effects; Down-Regulation - drug effects; Down-Regulation - genetics; Drug Evaluation, Preclinical; Gene Expression Regulation, Neoplastic - drug effects; Humans; Isoproterenol - pharmacology; NF-kappa B - genetics; NF-kappa B - metabolism; NF-kappa B - physiology; Propranolol - pharmacology; Receptors, Adrenergic, beta - genetics; Receptors, Adrenergic, beta - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - physiology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or_00001032

In a recent clinical observation, the growth of endothelial tumors, such as nasopharyngeal carcinoma, was repressed by the non-selective-adrenergic antagonist propranolol. In this study, we evaluated whether β-adrenoceptors (β-ARs), nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were involved in modulating cell apoptosis and cell cycle arrest by propranolol in human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) in vitro. Our results showed that the propranolol treatment inhibited cell proliferation in a concentration-dependent manner, suggesting the involvement of β-ARs in this cellular response. Propranolol-induced growth inhibition was associated with G0/G1 arrest and G2/M arrest depending upon the concentration. In addition, propranolol also induced apoptosis in both cell lines, as determined by Annexin V staining assay. Furthermore, propranolol decreased the level of NF-κB and then downregulated VEGF, Cox-2, MMP-2 and MMP-9 expression. Collectively, these results suggested that propranolol repressed gastric cancer cell growth through the inhibition of β-ARs and the downstream NF-κB-VEGF/MMP-2/9/COX-2 pathway.