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

        Ju Chae Park,Hyeon GyeungY oo,Hong Su Kim,Min A Jung,Mi Ha Kim,Sang Won Han,Kee Oh Chay,Boo Ahn Shin,Bong Whan Ahn,Young Do Jung 대한암학회 2002 Cancer Research and Treatment Vol.34 No.6

        Purpose: The role of P38 mitogen-activated proteinkinase (MAPK) in gastric cancer invasion has not yetbeen determined. In this study, we examined the effectsof SB203580, a specific P38 MAPK inhibitor, on the invitro invasion of gastric cancer and upon the moleculesinvolved in this process.Materials and Methods: Human gastric cancer SNU-638cells were maintained in RPMI 1640 supplemented with10% FBS. BIOCOAT matrigel invasion chambers wereused to examine in vitro invasiveness, zymography forgelatinase activity, CAT assay for uPA promoter activityand Western and Northern blotting to determine proteinand mRNA levels, respectively.Results: Treatment of SNU-638 cells with SB203580, aspecific P38 MAPK inhibitor, reduced in vitro invasiveness,dose-dependently. SB203580 treatment was foundto decrease both mRNA expression and uPA promoteractivity in gastric SNU-638 cells. In vitro invasion ofSNU-638 cells was partially abrogated by uPA-neutralizingantibodies. The activities of MMPs were not significantlyaltered by SB203580.Conclusion: Our results suggest that P38 MAPK is apotential therapeutic target for inhibiting uPA-dependentgastric tumor invasiveness and metastasis. (Cancer Res Treat. 2002;34:426-431)

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