Scutellaria barbata D. Don, a perennial herb belonging to the family Lamiaceae, is widely distributed throughout China and the Republic of Korea, and has been traditionally used in folk medicine as an antitumor and anti‑inflammatory agent. Polysaccharides isolated from Scutellaria barbata D. Don (PSB), have been reported to possess antitumor effects. However, the detailed antitumor mechanisms behind the effects of PSB remain unclear. In the present study, a non‑small cell lung cancer cell line harboring the HER2 gene mutation Calu‑3, the Calu‑3 cell line, was used to investigate the underlying mechanisms of the antitumor effects of PSB. The results revealed that PSB potently inhibited cell proliferation and human epidermal growth factor receptor (HER)2 phosphorylation in vitro, and also downregulated the expression of the downstream signaling molecules, including phosphorylated (phospho‑)Akt and phospho‑extracellular signal‑related kinase. In vivo, PSB demonstrated efficacy at well‑tolerated doses, including significant antitumor activity in a Calu‑3 subcutaneous xenograft model. Immunohistochemistry (IHC) analysis revealed a PSB dose‑dependent reduction of microvessel density, demonstrated by cluster of differentiation 31 staining. The present findings suggest that inhibition of tumor angiogenesis via suppression of the HER2 pathway may be one of the mechanisms by which PSB can be effective in the treatment of cancers.

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