|
|
Combined cimetidine and temozolomide, compared with
temozolomide alone: significant increases in survival in nude mice bearing
U373 human glioblastoma multiforme orthotopic xenografts
Lefranc F, James S, Camby I, Gaussin JF, Darro F, Brotchi J, Gabius J,
Kiss R
Department of Neurosurgery, Erasmus University Hospital, Belgium.
Object. Malignant gliomas consist of both heterogeneous proliferating and
migrating cell subpopulations, with migrating glioma cells exhibiting less
sensitivity to antiproliferative or proapoptotic drugs than proliferative
cells.
Therefore, the authors combined cimetidine, an antiinflammatory agent
already proven to act against migrating epithelial cancer cells, with
temozolomide to determine whether the combination induces antitumor
activities in experimental orthotopic human gliomas compared with the
effects of temozolomide alone.
Methods. Cimetidine added to temozolomide
compared with temozolomide alone induced survival benefits in nude mice with
U373 human glioblastoma multiforme (GBM) cells orthotopically xenografted in
the brain.
Computer-assisted phase-contrast microscopy analyses of 9L rat
and U373 human GBM cells showed that cimetidine significantly decreased the
migration levels of these tumor cells in vitro at concentrations at which
tumor growth levels were not modified (as revealed on monotetrazolium
colorimetric assay).
Computer-assisted microscope analyses of
neoglycoconjugate-based glycohistochemical staining profiles of 9L
gliosarcomas grown in vivo revealed that cimetidine significantly decreased
expression levels of endogenous receptors for fucose and, to a lesser
extent, for N-acetyl-lactosamine moieties.
Endogenous receptors of this
specificity are known to play important roles in adhesion and migration
processes of brain tumor cells.
Conclusions. Cimetidine, acting as an
antiadhesive and therefore an antimigratory agent for glioma cells, could be
added in complement to the cytotoxic temozolomide compound to combat both
migrating and proliferating cells in GBM.
PMID: 15871514 [PubMed - in process]
|
