Participation of MAPK and COX-2 in the Proliferative Process of Gastrointestinal Cancer Cells.

Accession number;03A0250906
Title;Participation of MAPK and COX-2 in the Proliferative Process of Gastrointestinal Cancer Cells.
Author; SASAKI EIJI (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) TOMINAGA KAZUNARI (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) SUTO REIKO (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) TAKASHIMA TAKASHI (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) HAMAGUCHI MASAKI (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) TANIGAWA TETSUYA (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) WATANABE TOSHIO (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) FUJIWARA YASUHIRO (Osakashidai Daigakuin Shokakikikanseigyonaikagaku) ARAKAWA TETSUO (Osakashidai Daigakuin Shokakikikanseigyonaikagaku)
Journal Title;Prog Med
Journal Code:F0664B
ISSN:0287-3648
VOL.23;NO.3;PAGE.847-850(2003)
Figure&Table&Reference;FIG.2, REF.6
Pub. Country;Japan
Language;Japanese
Abstract;Our previous study demonstrated the interaction between cyclooxygenase (COX)-2 and mitogen-activated protein kinase (MAPK) in terms of signal transduction pathways for proliferative process of rat normal gastric epithelial cells. Although overexpression of COX-2 is observed in some gastrointestinal cancer cells, significance of COX-2 during the proliferative process remain unclear. Therefore, we conducted the present study to evaluate the role of MAPK and COX-2 on cell proliferation in COX-2 expressing human gastrointestinal cancer cell lines. FBS (2, 5 and 10%, 24h) stimulated thymidine incorporation into both HT29 and MKN45 cells. In HT29 cell, pre-incubation with PD98059 (MAPK kinase inhibitor) or SB203580 (p38 MAPK inhibitor) and co-incubation with NS-398 (selective COX-2 inhibitor) or etodolac (selective COX-2 inhibitor) significantly inhibited cell proliferation. In MKN45 cell, pre-incubation with PD98059 or SB203580. but not co-incubation with NS398 or etodolac, significantly inhibited cell proliferation. FBS (5, 15 and 30 min) remarkably stimulated phosphorylated form of 3 kinds of MAPK (ERK, P38 MAPK, JNK) protein levels in both HT29 and MKN45 cells. FBS treatment for 6h remarkably increased expression of COX-2 protein in HT29 cell, although invariable in MKN45 cell. Our results suggest that MAPK plays an important role and COX-2 is not necessarily involved in the proliferative process of COX-2 expressing gastrointestinal cancer cells. (author abst.)