Involvement of p38-Beta MAPK in Cancer Cell Proliferation

Abstract

The original inflammation triggers an apoptosis through tumor necrosis factor alpha (TNF-α) induced mitogenactivated protein kinase (MAPK) pathway. However, a long-term subclinical inflammation might initiate a carcinogenesis, and this research investigates how the role of p38β in MAPK signaling pathway helps cell proliferation in tumor cell physiology. We used three cancer cell lines (Hela, Hep3B, PC3) to present three different types of antilogy carcinomas with strong proliferation abilities and discovered that the p38β replaces the original major expression protein p38α in MAPK signal pathway. Down stream cyclooxygenase-2 (COX2) expression enhances the cell proliferation of MAPK pathway. It was also controlled by p38β rather than p38α, and can be suppressed by the 24 h treatments of p38 MAPK inhibitor (SB203580, 5 μM) and p38β MAPK specific inhibitor (SB202190, 5 μM) in PC3 cells. Moreover, the treatments of 5 μM SB202190 successfully inhibited the PC3 cell proliferation within 24 h. All of the experimental evidences suggest that tumor cells caused by long-term inflammation can survive depending on a p38β MAPK replaced p38α MAPK signaling pathway and p38β might be a new cancer therapeutic target.