GKN2 increases apoptosis, reduces the proliferation and invasion ability of gastric cancer cells through down-regulating the JAK/STAT signaling pathway.
OBJECTIVE
To investigate the effect of gastric motility protein 2 (GKN2) on the proliferation, apoptosis and invasion of gastric cancer cell and on the JAK/signal transducer and activator of transcription 3 (STAT3) signaling pathway.


METHODS
Expression of GKN2 was qualified using Western blot analysis in four gastric cancer cell lines and immortalized human gastric mucosal epithelial cell line GES-1. The cells were then transfected with pcDNA3.1-GKN2 and control vector using Lipofectaminetm2000 and assayed for viability, apoptosis, cell cycle changes, invasion ability as well as expression of cell cycle protein D1 (Cylin D1), Bcl-2, Bax, matrix metalloproteinase 2 (MMP2), MMP9, JAK2 and p-STAT3.


RESULTS
Western blot analyses showed that the expression of GKN2 was significantly lower in 4 gastric cancer cell lines (BGC-823, SGC-7901, AGS and MKN-45) than in GES-1. Of them, SGC-7901 had the lowest expression. The line was chosen for subsequent transfection experiments. Compared with control (transfection with empty vector), pcDNA3.1-GKN2-transfected cells had significantly more GKN2 protein and mRNA, decreased cell viability, increased apoptosis, more cells arrested at G1 phase and reduced invasiveness. Expression analyses showed that expression of Cyclin D1, Bcl-2, MMP2, MMP9, JAK2 and STAT3 was significantly down-regulated, while Bax was significantly up-regulated.


CONCLUSIONS
Over-expression of GKN2 can increase apoptosis, reduce proliferation and invasion ability of gastric cancer cells as a result of down-regulated JAK2/STAT3 signaling pathway.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of South China Hunan, China.
Jun
J
Ouyang
Department of Urology, The First Affiliated Hospital of University of South China Hunan, China.
Xiaohui
X
Pan
Department of Pathology, University of South China Hunan, China.
Hui
H
Lin
Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of South China Hunan, China.
Zecheng
Z
Hu
Department of Pathology, University of South China Hunan, China.
Ping
P
Xiao
Department of Pathology, University of South China Hunan, China.
Haobin
H
Hu
Gastric motility protein 2; JAK/STAT3 signaling pathway; apoptosis; gastric cancer; invasion; proliferation