1. Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway.
- Author
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Qi X, Chen Y, Liu S, Liu L, Yu Z, Yin L, Fu L, Deng M, Liang S, and Lü M
- Subjects
- Animals, Humans, Mice, Antigens, CD metabolism, Cell Adhesion Molecules, Cell Line, Tumor, Cell Movement, Cell Proliferation, Mice, Nude, Molecular Docking Simulation, Phosphatidylinositol 3-Kinases metabolism, TOR Serine-Threonine Kinases metabolism, Melanoma drug therapy, Melanoma pathology, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Context: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo , 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. In vitro migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and in vivo 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 ( p < 0.05) with IC
50 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.- Published
- 2023
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