CISPLATIN BUT NOT BCNU INHIBITS UROKINASE-TYPE PLASMINOGEN-ACTIVATOR LEVELS IN HUMAN GLIOBLASTOMA CELL-LINES IN-VITRO

Glioblastomas extensively invade the surrounding normal brain tissue, with a concomitant expression of various proteolytic enzymes, in parti cular urokinase-type plasminogen activator (uPA), In this study we use d cis-diamminedichloroplatinum (cisplatin) and 1,3-bis(2-chloroethyl)- 1-nitrosourea (BCNU), commonly used anti-cancer drugs for the treatmen t of glioblastomas, to study the expression of uPA in three human glio blastoma cell lines in vitro, Cells were treated with 25 mu M cisplati n and 50 mu M BCNU, and uPA levels were estimated by fibrin zymography during a 72-h time course. Treatment of glioblastoma cells with cispl atin resulted in significantly decreased levels of uPA in serum-free c onditioned medium and cell extracts, compared to BCNU-treated and untr eated cell lines. Quantitative levels of uPA enzyme activity assessed by scanning laser densitometry and uPA protein by ELISA using antibody against uPA showed decreased levels of uPA in cisplatin-treated gliom a cell lines relative to BCNU and untreated cell lines, Our results su ggest that anti-tumor compound, cisplatin, may exert its anti-neoplast ic effects by inhibiting uPA in malignant glioblastomas.