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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.

Abstract
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 x 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. x 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. x 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.
AuthorsN Igarashi, T Kubota, Y Otani, S W Matsuzaki, M Watanabe, T Teramoto, K Kumai, K Tamaki, K Tanzawa, T Kobayashi, M Kitajima
JournalJapanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 90 Issue 1 Pg. 116-21 (Jan 1999) ISSN: 0910-5050 [Print] Japan
PMID10076574 (Publication Type: Journal Article)
Chemical References
  • Acetamides
  • Antineoplastic Agents
  • R 94138
  • Mitomycin
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Cisplatin
Topics
  • Acetamides (therapeutic use)
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Cisplatin (therapeutic use)
  • Gelatinases (antagonists & inhibitors)
  • Humans
  • Male
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases (antagonists & inhibitors)
  • Mice
  • Mice, Nude
  • Mitomycin (therapeutic use)
  • Neoplasm Metastasis (prevention & control)
  • Peritoneal Neoplasms (prevention & control, secondary)
  • Stomach Neoplasms (drug therapy, pathology, secondary)
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

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