Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway

• Published in: Brazilian journal of medical and biological research 2021-01, Vol.54 (2), p.e9017-e9017
• Main Authors: Yu, Renzhi, Wang, Miao, Wang, Minghuan, Han, Lei
• Format: Article
• Language: English
• Subjects: Animals; APAF-1 gene; Apaf-1 protein; Apoptosis; Apoptotic Protease-Activating Factor 1; BIOLOGY; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Caspase 3; Cell Line, Tumor; Cell Movement; Down-Regulation; ERK; Extracellular signal-regulated kinase; Gene expression; Gene Expression Regulation, Neoplastic; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; MAP Kinase Signaling System; MEDICINE, RESEARCH & EXPERIMENTAL; Melitten - pharmacology; Melittin; Mice; Neoplasm Invasiveness; Non-small cell lung carcinoma; NSCLC; Signal transduction; Small cell lung carcinoma; TGF-β; Transforming Growth Factor beta - metabolism
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431X20209017

The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-β expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-β overexpression (pTGF-β) abolished melittin-decreased TGF-β expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-β and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-β-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.