Sun Hao, Wang Gaolei, Ren Cong, Zhang Xi, Zhao Ping, Guo Bin
Shandong University of Traditional Chinese Medicine, Jinan, 250002, Shandong Province, China.
Lanling People's Hospital of Linyi City, 276000, Linyi, Shandong Province, China.
Sci Rep. 2025 May 6;15(1):15766. doi: 10.1038/s41598-025-99383-0.
Erianin, extracted from Dendrobium chrysotoxum Lindl, has shown significant antitumour activity in various cancers, including bladder, cervical, and nasopharyngeal carcinoma. This study explores Erianin's impact on melanoma, a prevalent intraocular malignancy in adults, emphasizing cell growth inhibition and its mechanism. Vascular endothelial growth factor-α (VEGF-α), a validated therapeutic target in uveal melanoma angiogenesis, was considered. Despite its origin from Dendrobium plants in the Orchidaceae family, Erianin's anti-melanoma effects and its potential to inhibit the PI3K/AKT/mTOR signalling pathway to decrease VEGF-α secretion in melanoma cells remain unexplored. Thus, Erianin's effects on A375 cells and its underlying molecular mechanisms were investigated. Erianin induced apoptosis in A375 cells, as demonstrated by flow cytometry and western blot assays. Additionally, Erianin inhibited A375 cell migration, proliferation, and invasion in vitro, evidenced by cell scratch, EdU stain, and transwell cell invasion assays. Mechanistically, Erianin downregulated VEGF-α and VEGF Receptor 2 expression while inhibiting PI3K/AKT pathway activation, indicated by western blot and immunofluorescence analyses. Furthermore, both western blot and immunofluorescence analyses confirmed Erianin's regulation of VEGF-α and VEGFR2 expression. This study suggests that Erianin is a novel compound capable of inducing cell apoptosis while suppressing the activation of the VEGF/PI3K/AKT signalling pathway in A375 cells, thereby inhibiting cell proliferation.
毛兰素是从金石斛中提取的,已在包括膀胱癌、宫颈癌和鼻咽癌在内的多种癌症中显示出显著的抗肿瘤活性。本研究探讨了毛兰素对黑色素瘤(一种成人中常见的眼内恶性肿瘤)的影响,重点研究其对细胞生长的抑制作用及其机制。血管内皮生长因子-α(VEGF-α)是葡萄膜黑色素瘤血管生成中已得到验证的治疗靶点,本研究对此进行了考量。尽管毛兰素源自兰科石斛属植物,但其对黑色素瘤的抗癌作用以及抑制PI3K/AKT/mTOR信号通路以减少黑色素瘤细胞中VEGF-α分泌的潜力仍未得到探索。因此,本研究调查了毛兰素对A375细胞的影响及其潜在分子机制。流式细胞术和蛋白质免疫印迹分析表明,毛兰素可诱导A375细胞凋亡。此外,细胞划痕、EdU染色和Transwell细胞侵袭实验证明,毛兰素在体外可抑制A375细胞的迁移、增殖和侵袭。从机制上讲,蛋白质免疫印迹和免疫荧光分析表明,毛兰素下调VEGF-α和VEGF受体2的表达,同时抑制PI3K/AKT通路的激活。此外,蛋白质免疫印迹和免疫荧光分析均证实了毛兰素对VEGF-α和VEGFR2表达的调节作用。本研究表明,毛兰素是一种新型化合物,能够诱导细胞凋亡,同时抑制A375细胞中VEGF/PI3K/AKT信号通路的激活,从而抑制细胞增殖。