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Original Article
- SB203580, a P38 MAPK Inhibitor, Blocks in vitro Invasion by Human Gastric SNU-638 Cells
- Ju Chae Park, Hyeon Gyeung Yoo, Hong Su Kim, Min A Jung, Mi Ha Kim, Sang Won Han, Kee Oh Chay, Boo Ahn Shin, Bong Whan Ahn, Young Do Jung
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Cancer Research and Treatment 2002;34(6): 426-431.
DOI: https://doi.org/10.4143/crt.2002.34.6.426
Published online: December 31, 2002
Chonnam National University Research Institute of MedicalSciences, Chonnam National University Medical School,Gwangju, Korea. ydjung@chonnam.ac.kr
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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.
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