Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
In Vivo. 2019 Nov-Dec;33(6):1901-1910. doi: 10.21873/invivo.11684.
BACKGROUND/AIM: Interleukin (IL)-1β is a pro-inflammatory cytokine that has recently been established as a stimulator of angiogenesis via regulation of proangiogenic factor expression in the tumor microenvironment. This study aimed to demonstrate the inhibitory effects of Robinia pseudoacacia leaf extract (RP) on IL-1β-mediated tumor angiogenesis.
Secreted embryonic alkaline phosphatase (SEAP) reporter gene assay, ex vivo and in vitro tube formation assay, western blot, and quantitative PCR were used to analyze the inhibitory effect of RP on IL-1β-mediated angiogenesis.
RP inhibited secretion of SEAP, blocked IL-1β signaling, and inhibited IL-1β-mediated angiogenesis in ex vivo and in vitro assays. RP inhibited nuclear translocation of NF-ĸB by suppressing phosphorylation of IL-1β signaling protein kinases and inhibited mRNA expression of IL-1β-induced pro-angiogenic factors including VEGFA, FGF2, ICAM1, CXCL8, and IL6.
RP suppressed IL-1β-mediated angiogenesis and, thus, could be a promising agent in anticancer therapy.
背景/目的:白细胞介素(IL)-1β是一种促炎细胞因子,最近已被确定为通过调节肿瘤微环境中促血管生成因子的表达来刺激血管生成。本研究旨在证明洋槐叶提取物(RP)对 IL-1β介导的肿瘤血管生成的抑制作用。
采用分泌型碱性磷酸酶(SEAP)报告基因检测、体外和体内管形成检测、Western blot 和定量 PCR 分析 RP 对 IL-1β介导的血管生成的抑制作用。
RP 抑制 SEAP 的分泌,阻断 IL-1β信号通路,并抑制体内外实验中 IL-1β介导的血管生成。RP 通过抑制 IL-1β信号蛋白激酶的磷酸化来抑制 NF-κB 的核易位,并抑制 IL-1β诱导的促血管生成因子包括 VEGFA、FGF2、ICAM1、CXCL8 和 IL6 的 mRNA 表达。
RP 抑制了 IL-1β介导的血管生成,因此可能成为癌症治疗的一种有前途的药物。