Open AccessInhibition of nuclear factor‐kappaB suppresses peritoneal dissemination of gastric cancer by blocking cancer cell adhesion
Author(s) -
Mino Kazuhiro,
Ozaki Michitaka,
Nakanishi Kazuaki,
Haga Sanae,
Sato Masanori,
Kina Masaya,
Takahashi Masato,
Takahashi Norihiko,
Kataoka Akihiko,
Yanagihara Kazuyoshi,
Ochiya Takahiro,
Kamiyama Toshiya,
Umezawa Kazuo,
Todo Satoru
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01901.x
Subject(s) - cancer cell , cancer , integrin , cancer research , cell adhesion , medicine , peritoneal cavity , cell , in vivo , adhesion , peritoneum , cell adhesion molecule , immunology , pathology , biology , chemistry , surgery , biochemistry , microbiology and biotechnology , organic chemistry
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. ( Cancer Sci 2011; 102: 1052–1058)