Lipoxin A(4) inhibited hepatocyte growth factor-induced invasion of human hepatoma cells.
OBJECTIVE
Inflammation is a critical component of tumor progression. Lipoxin A(4) (LXA(4)) has been approved for potent anti-inflammatory properties. Recently, it was reported that LXA(4) repressed the expression and activity of cyclooxygenase-2 (COX-2), which is essential for invasion. However, there are few reports dealing with its effects on cancer. To explore whether LXA(4) regulate invasion, the effects of LXA(4) and its receptor agonist BML-111 on hepatocyte growth factor (HGF)-induced invasion of hepatoma cells and the possible mechanisms were researched.


METHODS
Lipoxin A(4) receptor (ALX) expression in HepG2 cells were measured through reverse transcription polymerase chain reaction and western blot. Cytotoxicity of LXA(4) and BML-111 to HepG2 cells was detected by MTT and ((3)H)-TdR incorporation assay. Cell migration and invasion assays were performed using a Boyden chemotaxis chamber. COX-2 expression was detected by real-time polymerase chain reaction and western blot, respectively. Moreover, the expressions of matrix metalloproteinases (MMP)-2, MMP-9, IkappaBalpha and nuclear factor-kappaB (NF-kappaB) p65 were observed via western blot, and NF-kappaB transcriptional activity was tested by transfections and luciferase activities assay.


RESULTS
ALX expression was detected in HepG2 cells, and suitable concentrations of LXA(4) and BML-111 had no cytotoxicity to cells. LXA(4) and BML-111 inhibited HGF-induced migration and invasion; downregulated COX-2, MMP-2 and -9; restrained HGF-induced IkappaBalpha degradation, NF-kappaB translocation and the transcriptional activity of NF-kappaB in HepG2 cells. Furthermore, exogenous PGE2 could reverse the inhibitory effects of LXA(4) also BML-111 on HGF-induced invasion and migration partially.


CONCLUSIONS
LXA(4) inhibited HGF-induced invasion of HepG2 cells through NF-kappaB/COX-2 signaling pathway partially.
Zhou
Xiao-Yan
XY
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li
Yong-Sheng
YS
Wu
Ping
P
Wang
Hong-Mei
HM
Cai
Zhen-Yu
ZY
Xu
Fang-Yun
FY
Ye
Du-Yun
DY