Cancer Res Treat.  2002 Dec;34(6):426-431.

SB203580, a P38 MAPK Inhibitor, Blocks in vitro Invasion by Human Gastric SNU-638 Cells

• Park JC
• Yoo HG
• Kim HS
• Jung MA
• Kim MH
• Han SW
• Chay KO
• Shin BA
• Ahn BW
• Jung YD

Abstract

PURPOSE: The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process.
MATERIALS AND METHODS
Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively.
RESULTS
Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580.
CONCLUSION
Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis.

Keyword

Stomach neoplasm; P38 milogen-activated protein kinase; Urokinase-type plasminigen activator; Invasion

MeSH Terms

Animals
Antibodies
Blotting, Northern
Cats
Gelatinases
Humans*
Matrix Metalloproteinases
Neoplasm Metastasis
p38 Mitogen-Activated Protein Kinases*
Protein Kinases
RNA, Messenger
Stomach Neoplasms
Antibodies
Gelatinases
Matrix Metalloproteinases
Protein Kinases
RNA, Messenger
p38 Mitogen-Activated Protein Kinases