Octacosanol Suppresses Lung Cancer Metastasis and Angiogenesis via Targeting MMPs and VEGF

Natural bioactive compounds present promising avenues for the prevention and therapeutic intervention of cancer. Octacosanol has garnered significant attention for its distinctive biological properties, yet its specific antitumor effects and underlying mechanisms remain unclear. This study systematically evaluated its antitumor effects and elucidated the associated molecular mechanisms. We confirmed that it dose-dependently inhibited A549 cell proliferation in vitro. It also remarkably suppressed cell invasion and migration by downregulating MMP2 and MMP9 expression, an effect that was associated with reduced phosphorylation of JAK3/STAT3 and PI3K/AKT, suggesting a potential regulatory role of these signalling cascades. Meanwhile, it significantly inhibited tumor cell VEGF secretion and VEGF-mediated neoangiogenesis by modulating the PI3K/AKT signaling axis. Mouse experiments demonstrated that octacosanol significantly reduced tumor p-AKT, MMP2, and MMP9 levels, indicating its in vivo anti-metastatic effect. It also remarkably decreased tumor microvessel density, alongside reduced VEGF and vascular endothelial marker CD31 expression, further verifying its potent anti-angiogenic activity. This work provides evidence of octacosanol's dual anti-metastatic and anti-angiogenic effects in lung cancer and offers novel mechanistic insights into its activity against this highly prevalent malignancy. These findings establish a solid foundation for further exploration and development of octacosanol as a promising adjuvant for clinical antitumor therapy.