ANTI-INVASIVE ACTIVITY OF URSOLIC ACID CORRELATES WITH THE REDUCED EXPRESSION OF MATRIX METALLOPROTEINASE-9 (MMP-9) IN HT1080 HUMAN FIBROSARCOMA CELLS

We examined the anti-invasive activity of ursolic acid (UA) on the hig hly metastatic HT1080 human fibrosarcoma cell line, UA reduced tumor c ell invasion through a reconstituted basement membrane in a transwell chamber, A significant down-regulation of matrix metalloproteinase-9 [ MMP-9; M(r) 92,000 gelatinase/type IV collagenase (gelatinase B)] by U A was detected by Northern blot analysis, However, MMP-2 [M(r) 72,000 gelatinase/type IV collagenase (gelatinase A)] and membrane-type MMP w ere constantly expressed, and the expression of tissue inhibitor of me talloproteinase (TIMP)-1 and TIMP-2 also was not changed after 3 and 6 days of treatment with UA. Quantitative gelatin-based zymography conf irmed a markedly reduced expression of MMP-9 but not MMP-2 after treat ment with UA. To confirm the UA-induced down-regulation of MMP-9 expre ssion, we constructed a secreted alkaline phosphatase (SEAP) reporter vector including MMP-9 promoter, After transfection of MMP-9/SEAP repo rter vector into HT1080 cells, reduced SEAP activity was detected afte r treatment with UA, These results suggest that downregulation of MMP- 9 contributes to the anti-invasive activity of UA in HT1080 cells.