Hypocrellin A exerts antitumor effects by inhibiting the FGFR1 signaling pathway in non-small cell lung cancer

Abstract

BackgroundNon-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer, which is the deadliest form of cancer worldwide. Recent studies have shown that genes in the fibroblast growth factor (FGF) family are highly mutated in lung cancer, and fibroblast growth factor receptor 1 (FGFR1) has been found to be involved in various cancers, including lung cancer, suggesting that FGFR1 is a valid therapeutic target. Hypocrellin A (HA), a molecule with multiple biological activities, has been shown to influence cancer growth, but the specific mechanisms of its antitumor action have not been fully explored. MethodsMTT, colony formation, wound healing, transwell cell invasion and EdU cell proliferation assays were performed upon HA treatment of three NSCLC cell lines, H460, PC-9 and H1975. Hoechst 33258 staining and caspase 3 activity assays were carried out to investigate the impact of HA on apoptosis in these cells. Molecular docking and surface plasmon resonance were conducted to assess binding of HA to FGFR1. A mouse tumor model was used to detect the NSCLC-inhibitory ability of HA in vivo. ResultsThrough in vitro assays, HA was shown to negatively impact cell viability, migration, invasion and promote apoptosis in three human NSCLC cell line models. HA was shown to bind to FGFR1 and to inhibit its autophosphorylation and the phosphorylation of downstream signaling molecules. Inhibition of tumor growth was also demonstrated in a mouse xenograft tumor model, and no toxic effects of HA treatment were observed. ConclusionsHA inhibits the activity of the FGFR1 and STAT3 signaling pathways. HA thus represents a potential new FGFR1-targeted treatment for NSCLC.