title: In-vitro effect of a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) on human gastric cancer cell lines: timing of cisplatin treatment.
abstract: BACKGROUND
  To date, we have few effective chemotherapeutic agents against advanced and recurrent gastric cancer. 5-Fluorouracil (5-FU) and cisplatin (CDDP) are the most widely used drugs, and their combination has demonstrated favorable outcomes. However, the method (especially the timing) of CDDP administration is not well established.
  
  
  METHODS
  We examined the in-vitro effect of a combination of 5-FU and CDDP on four human gastric cancer cell lines: MKN-1, MKN-28, MKN-45, and MKN-74. The cell lines were exposed to 50% of the inhibitory concentrations of 5-FU and CDDP for 72 h and 8 h, respectively. CDDP was applied before, simultaneously with, and after the start of treatment with 5-FU.
  
  
  RESULTS
  When CDDP was applied after 5-FU, the cytotoxic activity against MKN-28, MKN-45, and MKN-74 was significantly potentiated. Against MKN-1, the earlier the initiation of CDDP treatment, the stronger was the cytotoxic effect.
  
  
  CONCLUSIONS
  Our results suggest that the cytotoxicity of a combination of 5-FU and CDDP against human gastric cancer cells is both cell-line- and schedule-dependent and is especially affected by the timing of the CDDP treatment.
authors.affiliation: First Department of Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Cho
authors.forename: Toshio
authors.initials: T
authors.lastname: Imada
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.forename: Manabu
authors.initials: M
authors.lastname: Shiozawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takanashi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D002945:Cisplatin; D005472:Fluorouracil