Open AccessMatrix Metalloproteinase Inhibitor, Marimastat, Decreases Peritoneal Spread of Gastric Carcinoma in Nude Mice
Author(s) -
Kimata Masaru,
Otani Yoshihide,
Kubota Tetsuro,
Igarashi Naoki,
Yokoyama Takeyoshi,
Wada Norihito,
Yoshimizu Nobunari,
Fujii Masato,
Kameyama Kaori,
Okada Yasunori,
Kumai Koichiro,
Kitajima Masaki
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01326.x
Subject(s) - matrix metalloproteinase , mitomycin c , medicine , matrix metalloproteinase inhibitor , cancer , chemotherapy , tissue inhibitor of metalloproteinase , carcinoma , pathology , cancer research , pharmacology , surgery
Marimastat, a matrix metalloproteinese inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK–1. Even with novel approaches such as molecular targeting of cancer chemotherapy, peritoneal dissemination of gastric cancer has little sensitivity to anticancer drugs, and it is impossible to inhibit its growth completely. Intraperitoneal injection of TMK–1 into nude mice at 5 × 10 5 cells/body resulted in carcinomatous peritonitis that mimicked clinical cases. Continuous administration of marimastat (18 mg/kg/day) from 24 h after the tumor inoculation successfully inhibited the growth of peritoneal dissemination nodules. Combined administration of marimastat (18 mg/kg/day) and mitomycin C (MMC, 2 mg/kg) showed synergistic inhibition of growth of peritoneal dissemination, being superior to MMC alone (2 mg/kg). Although marimastat alone could not increase survival tune with statistical significance, combined administration of marimastat and MMC had a survival benefit with statistical significance. The combination of marimastat and MMC increased the preventive effect on peritoneal dissemination. Marimastat seems to be a candidate for the prevention of peritoneal spread of gastric carcinoma.