Inhibition of organ invasion by the matrix metalloproteinase inhibitor XXXX ( @entity11556 ) in two @entity1 colon carcinoma metastasis models.

@entity1 @entity96 @entity5 @entity14 @entity11556
The effect of the matrix metalloproteinase inhibitor @entity11556 was evaluated in two @entity1 @entity14 models involving: (a) the @entity96 C170HM2 and (b) the lung-invasive @entity5 AP5LV, both of which have been shown to express the M(r) 72,000 type IV collagenase. @entity11556 at concentrations between 0.01 and 3.0 micrograms/ml had no direct cytotoxic effects on the in vitro growth of the cell lines. In the @entity96 model, @entity11556 administered i.p. from day 10 to termination of the therapy (day 39) at 40 mg/kg reduced both the mean number of @entity96 (35% of vehicle-treated control; P < 0.05) and the cross-sectional area of the @entity5 (43% of vehicle-treated control; P < 0.05). In the lung-invasive @entity5 model, @entity11556 administered daily (40 mg/kg i.p.) significantly reduced @entity5 weight within the lung (72% of vehicle-treated control; P < 0.05) but did not significantly affect nodule number. In the latter model, in which the take rate was unaffected, @entity5 cells were introduced into the lateral tail vein, and lung localization may have been a physical phenomenon not involving invasion. In the former model, @entity5 cells were introduced directly into the peritoneal cavity, and from there the cells adhered to and invaded the liver capsule. Because the take rate is significantly reduced, it may be that the matrix metalloproteinases are involved in this process. @entity11556 may be a therapeutic modality for the treatment of @entity14 .
