Abstract：
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
摘要：
黑色素瘤是一种源自黑素细胞的皮肤癌。黑色素瘤的全球发病率正在迅速上升,构成重大公共卫生挑战。确定有效的治疗剂对于解决这个日益严重的问题至关重要。天然产物已显示出有希望的抗肿瘤活性。在这项研究中,一种植物类黄酮，taxifolin,使用加权相关网络分析(WGCNA)结合连接图(CMAP)平台进行筛选。Taxifolin被证实抑制增殖，迁移,黑色素瘤A375和MV-3细胞通过促进凋亡而具有侵袭能力。此外,它抑制了黑色素瘤细胞的上皮-间质转化（EMT）过程。细胞药理学分析显示，紫杉素通过PI3K/AKT信号通路发挥对黑色素瘤的抑制作用，特别是通过下调p-PI3K和p-AKT的蛋白表达。值得注意的是,添加SC-79，PI3K/AKT信号通路的激活剂，逆转了taxifolin对细胞迁移和凋亡的影响。此外，体内实验表明，taxifolin治疗可以减缓小鼠肿瘤的生长，而没有明显的毒性作用。基于这些发现,taxifolin有望成为治疗黑色素瘤的潜在药物。
