Lung cancer is one of the most common malignancies as well as an increasing cause of cancer-related deaths. Nitric oxide (NO)-donor-ferulic acid (FA) hybrids, in our previous study, were designed and synthesized, which exhibited positive anti-cancer activities, especially one compound labelled as FXS-3. In this study, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed and revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells by inducing cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and suppressed the mitogen-activated protein kinase (MAPK), AKT/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by inhibiting MAPK, AKT/mTOR and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about NO-donor-FA hybrids.
PACAP-27 tyrosine phosphorylates mitogen activated protein kinase and increases VEGF mRNAs in human lung cancer cells
