Abstract

Stomach cancer is a leading malignant disease in many countries. Conventional combination chernotherapy approaches to advanced gastric cancer only produce paitial response and there has been no impact on patient survival from these approaches as well. Of several promising new approaches the combination of interferon (IFN) and chemotherapeutic agents are now being made to improve the effectiveness for the treatment of cancer. Preclinical studies suggested that IFN may biochemically modulate the cellular uptake or metabolism of 5-fluorouracil (5-FU) resulting in s synergistic antitumor effect. Based on these data, Wadler reparted a promising result with combina- tion of 5-FU and IFN-alpha in patients with advanced colorectal carcinoma. This study was conducted to investigate the combined effects af 5-FU and recombinant IFN- gamma at cellular level against four gastric carcinoma cell lines (SNU-1, SNU-5, SNU-16, and NCI-NB7). We used a semiautomated tetrazolium-based colorimetric (MTT) assay for cytotoxicity and an isobologram analysis to evaluate the effect of the combination. The experiment was perfor- med three times on each of the three cell lines. Only two experirnents for SNU-16 and NCI-N87 showed supraadditivity (p< 0.02). On isobologram plotted by the mean value of three experiments for each cell line, supraadditivity was suggested for only SNU-16 (p = 0.055). In conclusion, our result did not document in vitro synergy between 5-FU and IFN-gamma for gastric carcinoma cell lines but additivity within clinically achievable dose range. Because in vivo immunomodulatory effect of IFN-gamma on host is more important rather than antiproliferative effect, the combination of 5-FU and IFN gamma is expected to improve the treatment of advanced gastric cancer.

• Keywords: 5-Fluorouracil, Recombinant interferon-gamma, Gastric carcinoma cell lines