Quercetin Inhibits the Proliferation and Metastasis of Human Non-Small Cell Lung Cancer Cell Line: The Key Role of Src-Mediated Fibroblast Growth Factor-Inducible 14 (Fn14)/ Nuclear Factor kappa B (NF-κB) pathway.

Abstract

BackgroundQuercetin (Que) is reported to induce apoptosis of lung cancer cells. Src is closely related to the progression of non-small cell lung cancer (NSCLC) and can be modulated by Que in macrophages. In the current study, the interaction between Que and Src signaling in NSCLC cells was explored to explain the anti-NSCLC function of Que.Material/MethodsNSCLC cell line HCC827 was subjected to the administrations of Que at different concentrations. The effect of Que on tumor cell proliferation was detected using MTT and colony formation assays. Then the effect on the migration and invasion abilities was assessed using scratch and Transwell assays. At molecular level, the changes in Src/Fn14/NF-κB signaling were determined using western blotting assays. The role of Src in the function of Que was further explored by inducing the expression of Src gene in NSCLC cells before Que administration. The results of the in vitro assays were verified using a NSCLC mice model.ResultsQue inhibited the proliferation and anchorage-independent growth of NSCLC cells. Additionally, Que delayed in the gap closure rate in scratch assays and decreased the membrane-penetrating cell number in Transwell assays. At a molecular level, Que suppressed the expression of Src, which subsequently inhibited Fn14/NF-κB signaling. In in vivo assays, Que inhibited the growth of solid tumors. After the overexpression of Src in NSCLC cells, the anti-NSCLC effect of Que was blocked by inducing NSCLC proliferation and metastasis, and by activating Fn14/NF-κB signaling. Moreover, the induced level of Src promoted the growth and metastasis potential of solid tumors in mice.ConclusionsQue exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF-κB pathway both in vitro and in vivo.