Polygonatum sibiricum polysaccharides (PSP) are a traditional herbal medicine component with potential therapeutic effects on several diseases. The present study aimed to assess the role of PSP in the treatment of human prostate cancer using a PC‑3 cell line by Cell CK‑8, transwell and wound healing assays, then elucidate the potential underlying mechanisms by western blot and quantitative Real‑time RT‑PCR. Different concentrations of PSP were applied to PC‑3 cells, and the proliferation, invasion and migration of PC‑3 cells were demonstrated to be significantly inhibited with increasing concentrations of PSP. Additionally, cell apoptosis rate and expression of caspase‑3 increased with higher PSP concentrations, and the cell cycle was arrested in the S phase. Furthermore, it was demonstrated that the expression of the multidrug resistance‑1 gene and its encoded protein P‑glycoprotein in PC‑3 cells decreased following PSP treatment, suggesting that PSP may have the potential to reverse multidrug resistance in PC‑3 cells. The present study also evaluated the possible mechanism of PSP action on PC‑3 cells. The results revealed that phosphorylated P65, PI3K and AKT decreased in a concentration‑dependent manner. As key molecules in the NF‑κB and PI3K/Akt signaling pathways, this finding suggests that the potential mechanism of the effect of PSP on prostate cancer cells may involve simultaneous mediation of the PI3K/Akt and NF‑κB signaling pathways. The present study demonstrated that PSP inhibit the proliferation, invasion and migration of PC‑3 cells in vitro, as well as reverse MDR in these cells. The underlying mechanism may involve the simultaneous regulation of the PI3K/Akt and NF‑κB signaling pathways.

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