RESUMO
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.
RESUMO
Aim To detect the concentration of the no-vel marine fibrinolytic compound FGFC1 ( fungi fi-brinolytic compound 1 ) on Beagle dogs ’ plasma and tissue by high performance liquid chromatography ( HPLC) , and also to investigate the pharmacokinetics and tissue distribution in Beagle dogs with intravenous injection, and to evaluate the FGFC1 into medicinal. Methods Chromatographic column: HP-C18 ( 4. 6 mm × 250 mm,5 μm); the column temperature was 40℃;the mobile phase was acetonitrile -0. 1% triflu-oroacetic acid gradient elute, the flow rate of 1 mL· min-1; the ultraviolet detection wavelength was 265 nm. The dog plasma samples were collected at different intervals after intravenous injection of three different doses (7. 5, 5. 0, 2. 5 mg·kg-1 ) of FGFC1, and the concentration of FGFC1 in plasma and tissue was deter-mined by HPLC method for estimating pharmacokinetic parameters and tissue distribution. Results The pa-rameters of 7. 5, 5. 0, 2. 5 mg·kg-1 were as follows:its elimination half-life ( T1/2β) was ( 49. 035 ± 2. 171 ) , ( 48. 422 ± 2. 113 ) and ( 48. 811 ± 2. 372 ) min, respectively;the peak concentration was (56. 48 ± 6. 23 ) , ( 48. 63 ± 5. 53 ) , ( 13. 64 ± 2. 76 ) mg · L-1 , respectively;clearance rate ( CL ) was ( 0. 0062 ± 0. 0004 ) , ( 0. 0071 ± 0. 0008 ) and ( 0. 0092 ± 0. 0006) L·min-1 ·kg-1 , respectively; mean reten-tion time ( MRT ) was ( 28. 17 ± 1. 16 ) , ( 26. 23 ± 0. 35) and (28. 66 ± 0. 84) min, respectively. Tissue distribution revealed that FGFC1 could quickly distrib-uted into the heart, liver, spleen, lung, kidney, intes-tine, stomach, brain, intestine, testicle, urine and fe-ces. Interestingly, the highest drug (FGFC1) concen-tration level was detected in the liver. Conclusions The above study shows a good pharmacokinetic profile as well as a good tissue distribution, indicating a drug-gable nature of the structure. Therefore, we consider that FGFC1 is promising for further study.