Currently, patients with peritoneal dissemination of
gastric cancer must accept a poor prognosis because there is no standard effective
therapy. To inhibit peritoneal dissemination it is important to inhibit interactions between extracellular matrices (ECM) and cell surface
integrins, which are important for
cancer cell adhesion. Although
nuclear factor-kappa B (NF-κB) is involved in various processes in
cancer progression, its involvement in the expression of
integrins has not been elucidated. We used a novel NF-κB inhibitor,
dehydroxymethylepoxyquinomicin (DHMEQ), to study whether NF-κB blocks
cancer cell adhesion via
integrins in a
gastric cancer dissemination model in mice and found that DHMEQ is a potent suppressor of
cancer cell dissemination.
Dehydroxymethylepoxyquinomicin suppressed the NF-κB activity of human
gastric cancer cells NUGC-4 and 44As3Luc and blocked the adhesion of
cancer cells to ECM when compared with the control.
Dehydroxymethylepoxyquinomicin also inhibited expression of
integrin (α2, α3, β1) in in vitro studies. In the in vivo model, we injected 44As3Luc cells pretreated with DHMEQ into the peritoneal cavity of mice and performed peritoneal lavage after the injection of
cancer cells. Viable
cancer cells in the peritoneal cavities were evaluated sequentially by in vivo imaging. In mice injected with DHMEQ-pretreated cells and lavaged, live
cancer cells in the peritoneum were significantly reduced compared with the control, and these mice survived longer. These results indicate that DHMEQ could inhibit
cancer cell adhesion to the peritoneum possibly by suppressing
integrin expression.
Nuclear factor-kappa B inhibition may be a new therapeutic option for suppressing postoperative
cancer dissemination.