Pulsatilla saponin E suppresses viability, migration, invasion and promotes apoptosis of NSCLC cells through negatively regulating Akt/FASN pathway via inhibition of flotillin-2 in lipid raft.

Purpose: Pulsatilla saponins from pulsatilla chinensis (Bunge) Regel have potential anti-tumor activities to certain human cancers. However, the roles of pulsatilla saponin E separated from pulsatilla saponins in non-small cell lung cancer (NSCLC) have not been reported.

Materials and methods: After treating NSCLC cells by pulsatilla saponin E at different concentrations, cell viability was measured by MTT and CCK-8 assays, and cell migration, invasion and apoptosis were detected by scratch wound-healing, transwell and flow cytometry assays. The contents of free cholesterol (FC) and total cholesterol (TC) were measured by high performance liquid chromatography (HPLC). The expression levels of flotillin-1, flotillin-2, Akt, fatty acid synthase (FASN) were detected by qRT-PCR and Western blot assays.

Results: Pulsatilla saponin E suppressed viability, migration, invasion and promoted apoptosis of NSCLC cells followed by regulation of apoptosis-related proteins, reduced contents of FC and TC, and the expression levels of flotillin-1, flotillin-2, Akt, and FASN in a concentration-dependent manner. However, the inhibitory effects of pulsatilla saponin E on viability, migration, invasion of A549 cells and the expression levels of flotillin-1, flotillin-2, Akt, and FASN were reversed by flotillin-2 overexpression.

Conclusions: Our study revealed that pulsatilla saponin E suppressed migration, invasion and promoted apoptosis of NSCLC cells through negatively regulating Akt/FASN signaling pathway via the inhibition of flotillin-2 in lipid raft (LR). The current findings could be explored for developing a novel therapeutic drug for NSCLC treatment.