Combination effects of kinase inhibitors with anti-cancer drugs on scirrhous gastric carcinoma.

硬癌的预后极差。FGFR-2/K-Samii是一种酪氨酸激酶生长因子受体，在硬化性胃癌细胞上高表达。转化生长因子-β(转化生长因子-β)信号与胃癌远处转移密切相关。本研究的目的是阐明FGFR-2/K-SAMII抑制剂Ki23057或转化生长因子β受体(TβR)抑制剂Ki26894与抗癌药物TS 1(5-氟尿嘧啶类似物)联用对硬化性胃癌发生的影响。联合应用TS1和Ki23057比单独应用TS1更有效地减少原位肿瘤和LN转移。Ki26894+TS1给药组也比单独用药更有效地抑制肿瘤生长和减少LN转移。提示5-FU联合FGFR-2磷酸化抑制剂或T-β-R抑制剂具有协同抗肿瘤作用，在硬化性胃癌的治疗中具有较好的应用前景。

Scirrhous carcinomas carry an extreme poor prognosis. FGFR-2/K-samII, a tyrosine kinase growth factor receptor, is overexpressed on scirrhous gastric cancer cells. Transforming growth factor-β (TGFβ) signals are closely associated with the distant metastases of gastric cancer. The aim of this study is to clarify the effect of a FGFR-2/K-samII inhibitor, Ki23057, or a TGFβ receptor (TβR) inhibitor, Ki26894, in combination with anticancer drugs TS1 (a 5-fluorouracil analog), on the development of scirrhous gastric cancer. The combined administration of TS1and Ki23057 decreases orthotopic tumors as well as LN metastasis more effectively than TS1 alone. The Ki26894 plus TS1 administration group also significantly suppressed tumor growth and decreased LN metastasis more effectively than either alone. These findings suggested that the combined treatment with 5-FU and FGFR-2 phosphorylation inhibitor or TβR inhibitor produced synergistic anti-tumor effects, and appears therapeutically promising in scirrhous gastric carcinoma treatment.