Background:
Saponin of Schizocapsa plantaginea Hance I (SSPH I),a bioactive
saponin found in Schizocapsa plantaginea, exhibits significant anti-proliferation and antimetastasis
in lung cancer.
Objective:
To explore the anti-metastatic effects of SSPH I on non-small cell lung cancer
(NSCLC) with emphasis on epithelial-mesenchymal transition (EMT) both in vitro and vivo.
Methods:
The effects of SSPH I at the concentrations of 0, 0.875,1.75, and 3.5 μM on A549 and
PC9 lung cancer cells were evaluated using colony formation assay, CCK-8 assay, transwell
assay and wound-healing assay. The actin cytoskeleton reorganization of PC9 and A549 cells
was detected using the FITC-phalloidin fluorescence staining assay. The proteins related to
EMT (N-cadherin, E-cadherin and vimentin), p- PI3K, p- AKT, p- mTOR and p- ERK1/2 were
detected by Western blotting. A mouse model of lung cancer metastasis was established by utilizing
95-D cells, and the mice were treated with SSPH I by gavage.
Results:
The results suggested that SSPH I significantly inhibited the migration and invasion of
NSCLC cells under a non-cytotoxic concentration. Furthermore, SSPH I at a non-toxic concentration
of 0.875 μM inhibited F-actin cytoskeleton organization. Importantly, attenuation of
EMT was observed in A549 cells with upregulation in the expression of epithelial cell marker
E-cadherin and downregulation of the mesenchymal cell markers vimentin as well as Ncadherin.
Mechanistic studies revealed that SSPH I inhibited MAPK/ERK1/2 and
PI3K/AKT/mTOR signaling pathways.
Conclusion:
SSPH I inhibited EMT, migration, and invasion of NSCLC cells by suppressing
MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways, suggesting that the natural compound
SSPH I could be used for inhibiting metastasis of NSCLC.