Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model.
The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition.
Department of Surgery, Queen's Medical Centre, Nottingham, UK.
S A
SA
Watson
T M
TM
Morris
S L
SL
Parsons
R J
RJ
Steele
P D
PD
Brown
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000188:drug therapy* / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000150:complications*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D016513:Mice, SCID; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases