Abstract
Caveolin-1 is a scaffold protein of caveolae in the mucosa of the gastrointestinal tract and acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. Caveolin-1 stabilizes cell-cell and cell-matrix contacts and is a hallmark of a number of different types of human cancer, including gastric cancer. All-trans retinoic acid (ATRA), a derivative of vitamin A, has been demonstrated to exhibit tumor inhibitory effects in acute leukemia and certain types of solid tumor. In the present study, treatment with ATRA was demonstrated to inhibit the proliferation of gastric cancer cell line SGC7901, in a time- and dose-dependent manner. The markedly increased membrane localization of caveolin-1 was observed in the cells that were treated with 10 µmol/l ATRA for > 48 h. In addition, it was observed that treatment with ATRA was able to regulate the level of phosphorylation of extracellular signal-regulated kinase (ERK). Therefore, the SGC7901 cells were treated with a specific agonist of ERK/mitogen-activated protein kinase (MAPK) investigate whether ATRA mediated its effects via the ERK/MAPK signaling pathway. The results of the present study demonstrated that ATRA-induced increase in membrane localization of caveolin-1 was reversed by treatment with a specific agonist of ERK/MAPK. Together, these results suggest that ATRA exhibits anti-gastric cancer effects. ATRA may regulate the membrane localization of caveolin-1 in order to inhibit the proliferation of SGC7901 cells. These effects of ATRA may be mediated by inhibiting the activation of ERK/MAPK signaling pathway. These results contribute to the current knowledge on the potential use of ATRA as therapy for solid tumors and provide further insight into the potential molecular mechanisms of ATRA action.