The β-adrenoceptor antagonist, propranolol, induces human gastric cancer cell apoptosis and cell cycle arrest via inhibiting nuclear factor κB signaling.
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.
Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an JiaoTong University, Xi'an 710061, PR China.
Xinhua
X
Liao
Xiangming
X
Che
Wei
W
Zhao
Danjie
D
Zhang
Tieqiang
T
Bi
Guanghui
G
Wang
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D016328:NF-kappa B; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol