Department of Ophthalmology, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China.
Mol Med Rep. 2019 May;19(5):3642-3648. doi: 10.3892/mmr.2019.10026. Epub 2019 Mar 14.
Retinoblastoma is an intraocular malignant tumor that may severely affect vision and represents a life‑threatening disease in children. Arctigenin (ATG) is an active compound that exhibits numerous pharmacological activities, which is isolated from the seeds of greater burdock (Arctium lappa Linnaeus), a plant used in traditional Chinese herbal medicine. The present study aimed to investigate the effects of ATG on cancer progression by analyzing the retinoblastoma cell line Y79. ATG exhibited a significant inhibitory effect on the viability of Y79 cells in a dose‑dependent manner. Furthermore, treatment with ATG promoted apoptosis, and increased the protein expression levels of B‑cell lymphoma 2 (BCL‑2)‑associated X protein and decreased the protein expression levels of BCL‑2. Cell migration was suppressed following treatment with ATG, as assessed by Transwell migration assay. Furthermore, the protein expression levels of jagged‑1 (JAG1) were decreased, and various factors involved in the Notch signaling pathway, including the Notch intracellular domain (NICD), transcription factor HES (HES)5 and HES1 were downregulated following treatment with ATG. The decreased expression levels of JAG1 were restored in response to JAG1 overexpression, alongside increases in the protein expression levels of NICD, HES5 and HES1. Furthermore, overexpression of JAG1 partly restored the cell viability and migration suppressed following treatment with ATG. In addition, ATG‑induced apoptosis was reduced by JAG1 overexpression. Collectively, the present results suggested that ATG may serve as an antitumor compound by suppressing the proliferation and migration of retinoblastoma cells, inducing apoptosis, downregulating the protein expression levels of JAG1, and decreasing the activity of the Notch signaling pathway.
视网膜母细胞瘤是一种眼内恶性肿瘤，可能严重影响视力，是儿童的生命威胁性疾病。牛蒡子苷（ATG）是一种从传统中药牛蒡（Arctium lappa Linnaeus）种子中分离出来的活性化合物，具有多种药理活性。本研究旨在通过分析视网膜母细胞瘤细胞系 Y79 来研究 ATG 对癌症进展的影响。ATG 对 Y79 细胞的活力具有显著的抑制作用，呈剂量依赖性。此外，ATG 处理促进了细胞凋亡，并增加了 B 细胞淋巴瘤 2（BCL-2）相关 X 蛋白（BCL-2-Associated X Protein，Bax）的蛋白表达水平，降低了 BCL-2 的蛋白表达水平。用 Transwell 迁移实验评估，ATG 处理后抑制了细胞迁移。此外，ATG 处理后，锯齿状 1（Jagged-1，JAG1）的蛋白表达水平降低， Notch 信号通路中的各种因子，包括 Notch 细胞内结构域（Notch Intracellular Domain，NICD）、转录因子 HES5 和 HES1 的蛋白表达水平下调。JAG1 过表达可恢复 JAG1 的表达水平降低，并增加 NICD、HES5 和 HES1 的蛋白表达水平。此外，JAG1 过表达部分恢复了 ATG 处理后抑制的细胞活力和迁移。此外，JAG1 过表达可降低 ATG 诱导的细胞凋亡。综上所述，本研究结果表明，ATG 可能通过抑制视网膜母细胞瘤细胞的增殖和迁移、诱导细胞凋亡、下调 JAG1 的蛋白表达水平以及降低 Notch 信号通路的活性来抑制肿瘤生长，从而发挥抗肿瘤作用。
