Ouyang Qi, Tian Shengye, Zhou Hengyu, Mao Ying, Li Xiang, Yan Feng, Liu Ailong, Hu Xiang, You Changqiao, He Jun
Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, China.
The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Front Oncol. 2025 Jul 10;15:1583580. doi: 10.3389/fonc.2025.1583580. eCollection 2025.
Melanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis.
Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, imaging, immunohistochemistry.
We confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and HO-induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway , and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth.
Salidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.
黑色素瘤由黑素细胞的恶性转化引起。大量研究表明，红景天苷的酪醇成分可抑制酪氨酸酶活性。PI3K/Akt/mTOR信号通路在生物色素合成中起关键作用。然而，红景天苷如何通过调节PI3K/Akt/mTOR在黑色素瘤中发挥抗黑色素瘤作用仍知之甚少。本研究旨在探讨红景天苷对黑色素瘤中PI3K/Akt/mTOR的影响，其在调节黑色素生成中起作用。
网络药理学预测红景天苷可能通过调节黑色素合成功能和信号通路发挥抗黑色素瘤作用。进行斑马鱼全胚胎杂交、RT-qPCR、黑色素合成和肿瘤发生试验，以研究红景天苷在黑色素合成中的治疗效果。通过RT-qPCR、蛋白质免疫印迹、免疫荧光、成像、免疫组织化学研究红景天苷抗黑色素瘤活性的机制。
我们通过网络药理学证实红景天苷可能通过调节黑色素合成相关基因表达和PI3K/Akt途径发挥抗黑色素瘤作用。此外，红景天苷通过抑制氧化应激减缓斑马鱼胚胎和HO诱导的B16F10细胞中的黑色素合成。此外，我们确定了红景天苷通过PI3K/Akt/mTOR途径对抗黑色素合成的影响，蛋白质免疫印迹结果表明红景天苷增加了细胞核中Nrf2的表达，并抑制了mTOR的磷酸化和PI3K/Akt途径。最后，瘤内给药显示红景天苷抑制黑色素瘤生长。
红景天苷最有可能通过其抗氧化特性和下调PI3K/Akt/mTOR途径抑制黑色素合成和黑色素瘤发展。我们的结果可能为黑色素瘤的治疗提供一种新的治疗策略。
