Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway.

Context: Sanguinarine (SAG) is the most abundant constituent of (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice , suggesting its potential for cancer chemotherapy.

Objective: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma.

Materials And Methods: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice.

Results: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells ( < 0.05) with IC values of 2.378 μM and 2.719 μM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth.

Conclusions: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.