Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction.
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.
Nakajima
Koichi
K
Department of Surgery, Public Chikusa Clinic, Chikusa-cho, Shiso-gun, Hyogo 671-3221, Japan. aae62660@pop21.odn.ne.jp
Okita
Yutaka
Y
Matsuda
Shozo
S
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D013274:Stomach Neoplasms / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D002121:Calcium Channel Blockers; D062367:ortho-Aminobenzoates; C012293:tranilast; D005472:Fluorouracil