水苏碱通过 CXCR4/ERK 和 CXCR4/Akt 通路活性抑制星形细胞瘤细胞的活力和迁移。
Stachydrine suppresses viability & migration of astrocytoma cells via CXCR4/ERK & CXCR4/Akt pathway activity.
机构信息
Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
出版信息
Future Oncol. 2018 Jun;14(15):1443-1459. doi: 10.2217/fon-2017-0562. Epub 2018 Jun 6.
AIM
Pilocytic astrocytomas (PAs) are a common adolescent malignancy. We evaluated the effects of the betaine stachydrine on human PA cells as well as its associated molecular mechanism(s).
MATERIALS & METHODS: Various experiments assessing stachydrine's effects on the human PA cell line Res186 were performed.
RESULTS & CONCLUSION: Stachydrine dose-dependently suppressed proliferation and colony formation in Res186 cells with no such effect on normal astrocytes. Stachydrine downregulated CXCR4 transcription through enhancing IκBα-based NF-κB inhibition. Stachydrine promoted apoptosis and cyclin D1/p27-associated G0/G1 phase arrest in a CXCR4/ERK- and CXCR4/Akt-dependent manner. Stachydrine suppressed MMP-associated migration and invasiveness via inhibiting CXCR4/Akt/MMP-9/2 and CXCR4/ERK/MMP-9/2 pathway activity. Stachydrine inhibits the viability, migration and invasiveness of human PA cells via inhibiting CXCR4/ERK and CXCR4/Akt signaling.
目的
毛细胞星形细胞瘤（PA）是一种常见的青少年恶性肿瘤。我们评估了甜菜碱 stachydrine 对人 PA 细胞的作用及其相关的分子机制。
材料与方法
进行了各种实验来评估 stachydrine 对 Res186 人 PA 细胞系的作用。
结果与结论
stachydrine 呈剂量依赖性地抑制 Res186 细胞的增殖和集落形成，而对正常星形细胞没有这种作用。stachydrine 通过增强 IκBα 依赖性 NF-κB 抑制来下调 CXCR4 转录。stachydrine 通过 CXCR4/ERK 和 CXCR4/Akt 依赖性方式促进细胞凋亡和细胞周期蛋白 D1/p27 相关的 G0/G1 期阻滞。stachydrine 通过抑制 CXCR4/Akt/MMP-9/2 和 CXCR4/ERK/MMP-9/2 通路活性来抑制 MMP 相关的迁移和侵袭。stachydrine 通过抑制 CXCR4/ERK 和 CXCR4/Akt 信号通路来抑制人 PA 细胞的活力、迁移和侵袭。
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