Abstract
Background: Non-small-cell lung cancer (NSCLC) is associated with the highest morbidity and mortality rate, and chemotherapy is the primary therapy for NSCLC. However, the clinical outcome is still far from satisfactory. This study aimed to determine the effects and mechanisms of FNC on NSCLC. Results: FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner in vitro. Mechanistically, treatment of H460 cells with FNC inhibits Bcl-2 expression and potentiates Cytochrome C (Cyt-C) release, Bax and caspase-3 expression. In parallel, FNC inhibits tumor migration, invasion and metastasis in H460 cells by increasing E-cadherin protein levels and reducing the expression of VEGF, MMP-2, MMP-9 proteins. And murine models and mouse xenograft models also proved that FNC could significantly inhibit NSCLC tumor growth and metastasis with low toxicity. Finally, we also discovered that inhibition of DNMT3B expression is one of the important mechanisms of FNC inhibiting proliferation and metastasis of NSCLC cells. Conclusions: FNC induces apoptosis through the mitochondrial apoptotic pathway and represses tumor progression by targeting multiple proteins related to cell adhesion and invasion in vitro and in vivo. Meanwhile, FNC was involved in regulating DNA methylation. In summary, our results support the further development of FNC as potential therapeutics for clinical non-small cell lung cancer.
Correction to: Cypripedin, a phenanthrenequinone from Dendrobium densiflorum, sensitizes non-small cell lung cancer H460 cells to cisplatin-mediated apoptosis