Preventive Effect of Matrix Metalloproteinase Inhibitor, R‐94138, in Combination with Mitomycin C or Cisplatin on Peritoneal Dissemination of Human Gastric Cancer Cell Line TMK‐1 in Nude Mice

R‐94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK‐1. When the supernatant of a co‐culture of TMK‐1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP‐2 had been inhibited by R‐94138. When TMK‐1 was injected intraperitoneally (i.p.) into nude mice at 5×10(5) cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R‐94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. ×5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R‐94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. ×5 starting from 1 week after tumor injection. The combination of MMC and R‐94138 increased the preventive effect on peritoneal dissemination. R‐94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.