EFFECT OF CISPLATIN AND BCNU ON MMP-2 LEVELS IN HUMAN GLIOBLASTOMA CELL-LINES IN-VITRO

Matrix metalloproteinases (MMPs) play an important role in various phy siological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to dete rmine the effect of the antitumor compounds cis-dichlorodiammine plati num (ii) (cisplatin) and 1, 3 his (2-chloroethyl)-1-nitrosourea (BCNU) on 72-kDa type IV collagenase activity (MMP-2) in human gliomas. Huma n glioblastoma cell lines were treated with cisplatin (25 mu M), and B CNU (50 mu M), and the levels of MMP-2 were estimated in serum-free co nditioned medium and in cell extracts at different time intervals, Gel atin zymography revealed increased levels of MMP-2 in serum-free condi tioned medium and in cell extracts of untreated glioblastoma cell cult ures during a 72-h period, In contrast, MMP-2 levels were significantl y decreased in cisplatin-treated cells both in conditioned medium and cell extracts, However, no significant changes of MMP-2 levels were no ted in BCNU-treated cells. Quantitative analysis of MMP-2 enzyme activ ity by densitometry and amount of MMP-2 protein by ELISA showed signif icantly decreased levels of MMP-2 in cisplatin-treated cells compared to BCNU and untreated glioblastoma cells. The results indicate that de creased levels of MMP-2 might represent an additional mechanism by whi ch cisplatin provides its antineoplastic effects.