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 physiological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to determine the effect of the antitumor compounds cis-dichlorodiammine platinum (ii) (cisplatin) and 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU) on 72-kDa type IV collagenase activity (MMP-2) in human gliomas. Human glioblastoma cell lines were treated with cisplatin (25 microM), and BCNU (50 microM), and the levels of MMP-2 were estimated in serum-free conditioned medium and in cell extracts at different time intervals. Gelatin zymography revealed increased levels of MMP-2 in serum-free conditioned medium and in cell extracts of untreated glioblastoma cell cultures during a 72-h period. In contrast, MMP-2 levels were significantly decreased in cisplatin-treated cells both in conditioned medium and cell extracts. However, no significant changes of MMP-2 levels were noted in BCNU-treated cells. Quantitative analysis of MMP-2 enzyme activity by densitometry and amount of MMP-2 protein by ELISA showed significantly decreased levels of MMP-2 in cisplatin-treated cells compared to BCNU and untreated glioblastoma cells. The results indicate that decreased levels of MMP-2 might represent an additional mechanism by which cisplatin provides its antineoplastic effects.
Chintala
S K
SK
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Ali-Osman
F
F
Mohanam
S
S
Rayford
A
A
Go
Y
Y
Gokaslan
Z L
ZL
Gagercas
E
E
Venkaiah
B
B
Sawaya
R
R
Nicolson
G L
GL
Rao
J S
JS
D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D003720:Densitometry / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000737:chemistry; D018093:Gelatinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D016895:Culture Media, Serum-Free; D005780:Gelatin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D002945:Cisplatin; D002330:Carmustine