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