Propranolol and landiolol inhibit cell proliferation enhanced by noradrenaline in human lung adenocarcinoma cells

• Published in: Biomedical Research Vol. 45; no. 6; pp. 253 - 259
• Main Authors: TOMIHARI, Masahiro, ISHIKAWA, Masashi, IWASAKI, Masae
• Format: Journal Article
• Language: English
• Published: Japan Biomedical Research Press 17.11.2024; Japan Science and Technology Agency
• Subjects: A549 Cells; Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - pathology; Adrenergic beta-Antagonists - pharmacology; Autonomic nervous system; Beta blockers; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Growth factors; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical prognosis; Morpholines - pharmacology; Noradrenaline; Norepinephrine; Norepinephrine - pharmacology; Polymerase chain reaction; Prognosis; Propranolol; Propranolol - pharmacology; Sarcoma; Urea - analogs & derivatives; Urea - pharmacology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0388-6107; 1880-313X; 1880-313X
• DOI: 10.2220/biomedres.45.253

Previous clinical data have shown that perioperative β-blocker administration can improve lung cancer prognosis, possibly by blocking autonomic nervous system responses. This study aimed to investigate the anticancer mechanisms of the β-blockers propranolol and landiolol for human lung adenocarcinoma cells treated with noradrenaline. A549 human lung adenocarcinoma cells were exposed to each of the following alone or in combination for 2 h: medium only for naïve control; noradrenaline at a dose of 10 μmol/L; propranolol at 10 nmol/L; and landiolol at 1000 nmol/L. Cell proliferation was examined using a cell counting kit-8 assay and immunofluorescent staining of Ki67. qRT-PCR array was performed for Harvey rat sarcoma viral oncogene homolog (HRAS), transforming growth factor-beta receptor II (TGFBR2), and vascular endothelial growth factor A (VEGFA). Noradrenaline (N) showed enhanced cell proliferation compared to control, with higher Ki67 expression on immunostaining, higher HRAS and VEGFA expressions, and lower TGFBR2 expression in qRT-PCR, whereas N-propranolol and N-landiolol showed no significant changes. The present data indicated that perioperative administration of β-blockers might improve the post- operative prognosis of lung cancer via blockage of the adrenergic response.