Marine Drugs (Jan 2022)
FGFC1 Exhibits Anti-Cancer Activity via Inhibiting NF-κB Signaling Pathway in <i>EGFR</i>-Mutant NSCLC Cells
Abstract
FGFC1, an active compound isolated from the culture of marine fungi Stachybotrys longispora FG216, elicits fibrinolytic, anti-oxidative, and anti-inflammatory activity. We have previously reported that FGFC1 inhibited the proliferation, migration, and invasion of the non-small cell lung cancer (NSCLC) cells in vitro. However, the precise mechanisms of FGFC1 on NSCLC and its anti-cancer activity in vivo remains unclear. Hence, this study was focused to investigate the effects and regulatory mechanisms of FGFC1 on two NSCLC cell lines, EGFR-mutant PC9 (ex19del) and EGFR wild-type H1299. Results suggested that FGFC1 significantly inhibited proliferation, colony formation, as well as triggered G0/G1 arrest and apoptosis of PC9 cells in a dose- and time-dependent manner, but no obvious inhibitory effects were observed in H1299 cells. Subsequently, transcriptome analysis revealed that FGFC1 significantly down-regulated 28 genes related to the NF-κB pathway, including IL-6, TNF-α, and ICAM-1 in the PC9 cells. We further confirmed that FGFC1 decreased the expression of protein p-IKKα/β, p-p65, p-IκB, IL-6, and TNF-α. Moreover, NF-κB inhibitor PDTC could strengthen the effects of FGFC1 on the expression of CDK4, Cyclin D1, cleaved-PARP-1, and cleaved-caspase-3 proteins, suggesting that the NF-κB pathway plays a major role in FGFC1-induced cell cycle arrest and apoptosis. Correspondingly, the nuclear translocation of p-p65 was also suppressed by FGFC1 in PC9 cells. Finally, the intraperitoneal injection of FGFC1 remarkably inhibited PC9 xenograft growth and decreased the expression of Ki-67, p-p65, IL-6, and TNF-α in tumors. Our results indicated that FGFC1 exerted anti-cancer activity in PC9 cells via inhibiting the NF-κB signaling pathway, providing a possibility for FGFC1 to be used as a lead compound for the treatment of NSCLC in the future.
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