Abstract
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.
MeSH Terms
Animals
Antineoplastic Agents/therapeutic use
Ascitic Fluid/drug therapy,prevention & control
Colorectal Neoplasms/complications
Drug Screening Assays, Antitumor
Female
Humans
Metalloendopeptidases/antagonists & inhibitors
Mice
Mice, SCID
Phenylalanine/analogs & derivatives,therapeutic use
Thiophenes/therapeutic use
Tumor Cells, Cultured
Chemicals
Antineoplastic Agents
Thiophenes
Phenylalanine
batimastat
Metalloendopeptidases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Watson S A
Department of Surgery, Queen's Medical Centre, Nottingham, UK.
Morris T M
Parsons S L
Steele R J
Brown P D
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