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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.

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