Saikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells by inhibiting the STAT3 pathway

OBJECTIVE: To study the effects of saikosaponin D (SSD) on proliferation and apoptosis in human non-small cell lung cancer cell lines, and to explore underlying mechanisms. METHODS: Following treatment with saikosaponin D, A549 and H1299 cells were assessed for anti-proliferation effects using cell cycle kit-8 assays, changes in nuclear morphology using 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell apoptosis using annexin V/propidium iodide double staining. Proliferation- and apoptosis-related proteins were detected by immunoblotting. RESULTS: Saikosaponin D had dose-dependent inhibitory effects on A549 cells (IC(50), 3.57 µM) and H1299 cells (IC(50), 8.46 µM). DAPI staining revealed decreased cell numbers, and most H1299 cells became round after treatment with 20 µM saikosaponin D. As saikosaponin D concentration increased, the proportions of cells in G0/G1 phase, and cells undergoing apoptosis, increased. Levels of phosphorylated p44/42 and signal transducer and activator of transcription (STAT)3 were significantly downregulated in both cell lines, while total STAT3 levels were not significantly affected. The cleaved form of caspase 3 was significantly upregulated. CONCLUSIONS: Saikosaponin D inhibits proliferation, inducing cell cycle arrest and apoptosis, in lung cancer cells in a dose-dependent manner, possibly through inhibition of STAT3 phosphorylation and activation of caspase 3.