Department of Respiratory Medicine, Mudanjiang Medical University Affiliated Hongqi Hospital, Mudanjiang, China.
Community Health Service Center, Mudanjiang Medical University Affiliated Hongqi Hospital, Mudanjiang, China.
Braz J Med Biol Res. 2020 Dec 18;54(2):e9017. doi: 10.1590/1414-431X20209017. eCollection 2020.
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.
本研究旨在探讨蜂毒素对非小细胞肺癌（NSCLC）细胞生长、迁移、侵袭和凋亡的抗癌作用。本研究还探讨了蜂毒素在 NSCLC 细胞中的潜在抗癌机制。结果表明，蜂毒素在体外抑制 NSCLC 细胞的生长、迁移和侵袭，并诱导其凋亡。蜂毒素增加了促凋亡 caspase-3 和 Apaf-1 基因的表达。蜂毒素抑制了肿瘤生长因子（TGF）-β的表达和 NSCLC 细胞中磷酸化 ERK/总 ERK（pERK/tERK）。然而，TGF-β过表达（pTGF-β）消除了蜂毒素对 NSCLC 细胞中 TGF-β表达和 pERK/tERK 的抑制作用。体内观察 120 天期间，蜂毒素治疗抑制了肿瘤生长并延长了小鼠的存活时间。与对照组相比，蜂毒素治疗增加了 TUNEL 阳性细胞的数量，并降低了肿瘤组织中 TGF-β和 ERK 的表达水平。总之，本研究结果表明，蜂毒素通过下调 TGF-β 介导的 ERK 信号通路抑制 NSCLC 细胞的生长、迁移和侵袭，并诱导其凋亡，提示蜂毒素可能是 NSCLC 治疗的一种有前途的抗癌药物。
