FGFC1 Inhibits Proliferation and Migration of Non-Small Cell Lung Cancer Cells via the PI3K/Akt/mTOR Signaling Pathway / 中国生物化学与分子生物学报

ABSTRACT

FGFC1 (Fungi fibrinolytic compound1) is a bisindole compound with good biological activity, which was first derived from the Stachybotrys longispora FG216. However, the anti-tumor effects of FGFC1 have not been reported. This study investigated the effect and mechanism of FGFC1 on the proliferation, apoptosis, migration and invasion of non-small cell lung cancer (NSCLC) cells.Firstly, PC9, H1975, HCT116, HeLa and 293T cells were treated with different concentrations of FGFC1, and the cell counting kit-8 assay was used to determine relative cell viability; flow cytometry was used to evaluate apoptosis; real-time PCR and Western blotting analysis were performed to measure the expression of apoptosis-related genes in PC9 cells; wound healing and Transwell invasion assays were used to measure the ability of migration and invasion; Western blotting was performed to measure the expression of kinase proteins involved in the PI3K/Akt/mTOR signaling pathway, exploring the influence of FGFC1 on this signaling pathway. We found that FGFC1 selectively inhibited the proliferation of PC9 cells. It also up-regulated the expression of apoptosis-promoting protein cleaved-caspase-3 and cleaved-PARP, and induced apoptosis in a dose-dependent manner (P < 0. 05). FGFC1 also significantly inhibited the migratory and invasive capacity of PC9 cells in a dose-dependent manner (P < 0. 05). Further studies confirmed that FGFC1 could inhibit the activation of the PI3K/Akt/mTOR signaling pathway with the down-regulation of the protein expression levels of p-PI3K, p-Akt and p-mTOR. Thus, we conclude that FGFC1 inhibited the proliferation of PC9 and H1975 cells, induced the apoptosis and inhibited the migration and invasion of PC9 cells, which may take place through down-regulating the PI3K/Akt/mTOR signaling pathway. These findings suggest that FGFC1 might be a new therapeutic target in NSCLC treatment in the future.