In vitro studies showed that decorin, a small proteoglycan that is a normal component of the cell matrix involved in tissue scaffolding, effectively inhibited the growth of two ovarian cancer lines, SKOV3 and 2774. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to measure cell growth, IC50s for decorin ranged from 150 to 400 microg/ml for the two cell lines. In contrast, the growth of tumor cells grown on an artificial cell matrix (Matrigel) was unaffected by decorin treatment, perhaps because of the decorin being irreversibly bound by matrix-associated collagen. Decorin-induced inhibition of ovarian tumor cells appeared to be associated with the increased expression of the cyclin-dependent kinase inhibitor p21Waf1/Cip1. Up-regulation of p21 expression was shown by Western blot analysis in decorin-treated ovarian cancer cells. No decorin-induced up-regulation of c-myc was seen, although decorin was reported to activate the epidermal growth factor receptor. Decorin was also shown to synergize with carboplatin to inhibit the growth of ovarian tumor cells. Additional studies are warranted to determine the role of decorin in the treatment of ovarian cancer.