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 inject ion of C170HM(2) cells into the peritoneal cavity of sCID mice and res ulted in solid tumour deposits and ascites formation. The cell line ex pressed both the 72 and 92 kDa forms of gelatinase by zymography. Bati mastat administered from day 0 (40 mg kg(-1)) reduced the volume of as cites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly redu ced to 77% of vehicle control when batimastat was administered From da y 0 (P<0.01) and 69% of control when administered from day 10 (P < 0.0 5). Thus, batimastat has the ability to reduce the volume of ascites f orming in SCID mice injected intraperitoneally with the human colorect al cell line, C170HM(2), when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in bo th treatment groups, highlighting the therapeutic potential of batimas tat in this clinical condition.