血根素(SAG) 是黄杨菜(Macleaya cordata (Willd.) R. Br. (Popaceae)) 中含量最丰富的成分。之前已在小鼠体内展示出SAG对于乳腺癌和结肠癌的转移有抗作用，表明它在癌症化疗中具有潜力。本研究旨在探究SAG对于黑色素瘤的抗转移作用及其分子机制。采用CCK8实验检测SAG对A375和A2058细胞增殖的抑制作用，应用网络药理学分析构建化合物-靶标网络并选择SAG抗黑色素瘤的潜在治疗靶点。进一步通过分子对接模拟对所选靶点进行分析，在1、1.5、2μM浓度下进行体外迁移/侵袭/西方印迹实验，以及2、4、8mg/kg浓度下进行裸鼠异种移植瘤模型的体内作用实验。SAG治疗黑色素瘤的关键靶点主要富集在PI3K-AKT信号通路上，SAG与PI3K、AKT、mTOR结合能分别为-6.33、-6.31、-6.07 kcal/mol。SAG的处理抑制了A375和A2058细胞的增殖、迁移和侵袭能力(p<0.05)，IC50值分别为2.378μM和2.719μM。同时，还降低了FAK、PI3K、AKT、mTOR的磷酸化水平，以及MMP2和ICAM-2的蛋白表达水平。在裸鼠异种移植瘤模型中，2、4、8mg/kg的SAG均能有效抑制肿瘤生长。本研究为SAG的临床抗肿瘤特性提供了理论基础，进一步表明了其在临床应用中的潜力。

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.To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma.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.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 IC50 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.Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.