食品科学

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蜂胶中CAPE对HGF诱导的HepG2细胞侵袭和迁移能力的抑制作用

王紫燕1,2,王莹莹1,2,曾晓雄1,张红城1,2,*   

  1. 1.南京农业大学食品科技学院,江苏 南京 210095;2.中国农业科学院蜜蜂研究所,北京 100093
  • 出版日期:2017-01-15 发布日期:2017-01-16

Inhibition of Caffeic Acid Phenethyl Ester (CAPE) Derived from Propolis on HGF-Induced Migration and Invasion of HepG2 Cells

WANG Ziyan1,2, WANG Yingying1,2, ZENG Xiaoxiong1, ZHANG Hongcheng1,2,*   

  1. 1. College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China;
    2. Bee Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100093, China
  • Online:2017-01-15 Published:2017-01-16

摘要: 目的:探讨咖啡酸苯乙酯(phenethyl caffeate,CAPE)对肝细胞生长因子(hepatocyte growthfactor,HGF)诱导的人肝癌细胞系(HepG2细胞)侵袭和迁移的抑制作用及机制。方法:将实验分为对照组(HGF=0 ng/mL;CAPE= 0 μ m o l /L)、诱导组(HGF=20 ng/mL;CAPE= 0 μ m o l /L)和荷药组(HGF=20 ng/mL;CAPE分别为2.5、5.0、7.5、10.0 μmol/L),测定细胞黏附率,Transwell小室模拟细胞侵袭和迁移能力以及划痕实验测定细胞迁移率,蛋白免疫印迹(Western blot)法检测ELMO1、MAP4K4和FNDC3B表达。结果:与对照组比较,诱导组表现出显著的促进细胞黏附和迁移作用,荷药组中表现出对HGF诱导的细胞黏附和迁移具有显著的抑制作用(P<0.05)。Transwell小室实验结果表明CAPE对HGF诱导的HepG2细胞侵袭和迁移作用有抑制作用。Western blot结果显示,诱导组和对照组相比ELMO1和MAP4K4表达显著上调,荷药组和诱导组相比ELMO1和MAP4K4表达显著下调(P<0.05);诱导组表达FNDC3B较对照组显著下降(P<0.05),荷药组FNDC3B表达量较诱导组增加,但结果不显著(P>0.05)。结论:CAPE能够抑制HGF诱导的HepG2细胞的黏附、侵袭和迁移。CAPE通过上调FNDC3B和下调ELMO1、MAP4KE的表达,抑制HepG2细胞的侵袭和迁移能力。

关键词: 咖啡酸苯乙酯, 细胞侵袭, 细胞迁移, ELMO1, MAP4K4, FNDC3B

Abstract: Objective: To explore the inhibitory effect and underlying molecular mechanism of caffeic acid phenethyl
ester (CAPE), a major component of propolis, on the hepatocyte growth factor (HGF)-induced migration and invasion of
human hepatocarcinoma (HepG2) cell lines. Methods: The experimental cells were divided into control (HGF = 0 ng/mL;
CAPE = 0 μmol/L), induction group (HGF = 20 ng/mL; CAPE = 0 μmol/L), and medication groups (HGF = 20 ng/mL;
CAPE = 2.5, 5.0, 7.5, or 10.0 μmol/L). The cell adhesion rate was determined, simulated cell invasion and migration were
evaluated by Transwell chambers and cell migration rate was measured by wound healing assay. The expression levels
of ELMO1, MAP4K4 and FNDC3B were detected by Western blot assay. Results: Compared with the control group, the
induction group showed that HGF can significantly promote cell adhesion and migration, and CAPE can significantly inhibit
the HGF-induced adhesion and migration of HepG2 cells (P < 0.05). The results of Transwell chamber experiments showed
that CAPE could inhibit the HGF-induced invasion and migration of HepG2 cells. Western blot results showed that the
expression of ELMO1 and MAP4K4 in the induction group was significantly up-regulated when compared with the control
group, while a significant down-regulation was observed for the expression of ELMO1 and MAP4K4 in the medication
group when compared with the induction group (P < 0.05). The FNDC3B expression in the induction group was significantly
decreased compared with the control group (P < 0.05), while the medication group was higher but not significantly than the
induction group (P > 0.05). Conclusion: CAPE can inhibit the HGF-induced adhesion, invasion and migration of HepG2
cells. CAPE inhabits HepG2 cells invasion and migration by up-regulating the expression of FNDC3B protein and downregulating
the expression of ELMO1 and MAP4KE protein.

Key words: caffeic acid phenethyl ester (CAPE), cell migration, cell invasion, ELMO1, MAP4K4, FNDC3B

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