Schisandrin C suppresses melanoma growth and metastasis through modulation of Rap1-related and phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathways.

Abstract

Schisandrin C (Sch C), a lignan derived from Schisandra chinensis , exhibits antitumor activity in several malignancies; however, its effects on melanoma remain unclear. This study investigated the antitumor effects of Sch C on melanoma growth and metastasis and the underlying molecular mechanisms. Network pharmacology was used to predict potential targets of Sch C. In-vitro assays using B16-F10 melanoma cells evaluated proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). In-vivo antitumor activity was assessed in a murine melanoma xenograft model. Protein expression of key signaling molecules was analyzed by Western blotting and immunohistochemistry. Sch C significantly inhibited melanoma cell proliferation, migration, and invasion in a dose-dependent manner and promoted apoptosis. Sch C downregulated EMT-related proteins, including matrix metalloproteinase (MMP)-2, MMP-9, and vimentin, while upregulating E-cadherin. Mechanistically, Sch C reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mechanistic target of rapamycin (mTOR) and was associated with modulation of Rap1-related signaling pathways. In vivo , Sch C markedly reduced tumor volume and weight without obvious toxicity and increased apoptosis while decreasing proliferation in tumor tissues. Sch C exerts antimelanoma effects and is associated with inhibition of PI3K/AKT/mTOR signaling and modulation of Rap1-related pathways, suggesting its potential as a therapeutic candidate for melanoma.