Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction

Abstract

Scirrhous gastric cancer is resistant to chemotherapy in comparison to other types of gastric cancers, and cancer cell-stromal fibroblast interactions play an important role in progression of scirrhous gastric cancer. We examined the effect of cancer cell-stromal fibroblast interactions on the sensitivity of an in vitro scirrhous gastric cancer model to the chemotherapeutic agent 5-FU. The model consisted of a human scirrhous gastric cancer cell line, KATO-III, and a human fibroblast cell line, KMST-6, maintained in collagen gel droplet cultures. KATO-III cell sensitivity to 5-FU was significantly decreased in co-cultures with KMST-6. KMST-6 cell sensitivity to 5-FU was also decreased in co-cultures with KATO-III. The addition of tranilast alone inhibited KMST-6, but not KATO-III, cell proliferation. In combination with 5-FU, tranilast significantly enhanced KATO-III cell sensitivity to 5-FU. These results suggest that (i), scirrhous gastric cancer cell sensitivity to 5-FU is decreased by the interactions between the cancer cells and stromal fibroblasts and (ii), tranilast enhances the sensitivity of scirrhous gastric cancer cell to 5-FU by inhibiting stromal fibroblast proliferation.