Combination effect of a TGF-β receptor kinase inhibitor with 5-FU analog S1 on lymph node metastasis of scirrhous gastric cancer in mice

摘要: Transforming growth factor-β (TGF-β) signals are closely associated with the distant metastases of gastric cancer. The aim this study was to clarify effect a TGF-β receptor I (TβR-I) phosphorylation inhibitor, Ki26894, in combination anticancer drugs, on lymph node (LN) metastasis scirrhous A novel TβR-I kinase inhibits Smad2 at ATP binding site TβR-I. S1 is 5-fluorouracil analog. human cancer cell line OCUM-2MLN and fibroblasts NF-33 were used. OCUM-2MLM cells upper well lower co-incubated or without Ki26894. proliferation significantly stimulated by co-culture cells. Ki26894 suppressed interactions between Gastric models established orthotopic inoculation showed diffusely infiltrating adenocarcinoma accompanied LN metastases. We divided these mice into four groups, (control vehicle, S1, plus S1), examined and/or Smad2, tumor size, metastases, lymphatic involvements. inhibited decreased extent involvement, compared control only group. administration group more effectively than either alone. These findings suggested that inhibitor useful for treatment carcinoma metastasis. (Cancer Sci 2010)