Abstract

Many in vitro studies or clinical trials reported synergistic effect of the combination of 5-FU and alpha-interferon 2a(IFNa-2a) in patients with colorectal cancer, urinary bladder cancer, and esophageal cancer. There have been few reports on the effects of the combination of 5-FU and IFN against gastric cancer ce11 lines. This study was conducted to investigate the com- bined cytotoxic effects of 5-FU or cisplatin with IFNa-2a against two gastric cancer cell lines. SNU-1 and SNU-l6 cell lines were treated with a serial concentrations of 5-FU plus IFNa-2a (5000: 1, molar ratio) and cisplatin plus IFNa-2a (400: 1, molar ratio). Cytotoxicity was determined using a tetrazolium-based colorimetric (MTT) assay. The combination effect of two drugs was evaluated by the median effect principle after Chou et aL Calculation of Assay-AUC was done after Park et aL In SNU-1 cell line, combination of 5-FU and IFNa-2a showed a synergistic effect (combination index, CI<1). Assay AUC of 5-FU was markedly reduced com- parable to clinically achievable-AUC in all combinations. In SNU-16 cell line, combination of 5- FU or cisplatin with IFNa-2a showed no synergism (CI> 1). But inhibitory concentration (IC ) value was markedly reduced. So 5-FU or cisplatin activity were markedly enhanced by IFNa- 2a, especially at low doses.

• Keywords: 5-FU, IFNa-2a, Synergistic antitumor effects, Gastric cancer