Περίληψη:
Matrix metalloproteinase 9 (MMP-9) is known to play a major role in cell
migration and invasion in both physiological and pathological processes.
Our previous work has shown that increased MMP-9 levels are associated
with human glioma tumor progression. In this study, we evaluated the
ability of an adenovirus containing a 528 bp cDNA sequence in antisense
orientation to the 5’ end of the human MMP-9 gene (Ad-MMP-9AS) to
inhibit the invasiveness and migratory capacity of the human
glioblastoma cell line SBN19 in in vitro and in vivo models. Infection
of glioma cells with Ad-MMP-9AS reduced MMP-9 enzyme activity by
approximately 90% compared with mock- or Ad-CMV-infected cells.
Migration and invasion of glioblastoma cells infected with Ad-MMP-9AS
were significantly inhibited relative to Ad-CMV-infected controls in
spheroid and Matrigel assays. Intracranial injections of SNB19 cells
infected with Ad-MMP-9AS did not produce tumors in nude mice. However,
injecting the Ad-MMP-9AS construct into subcutaneous U87MG tumors in
nude mice caused regression of tumor growth. These results support the
theory that adenoviral-mediated delivery of the MMP-9 gene in the
antisense orientation has therapeutic potential for treating gliomas.
Συγγραφείς:
Lakka, SS
Rajan, M
Gondi, C
Yanamandra, N
Chandrasekar,
N
Jasti, SL
Adachi, Y
Siddique, K
Gujrati, M and
Olivero, W
Dinh, DH
Kouraklis, G
Kyritsis, AP
Rao, JS
