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In vitro effects of topotecan and ionizing radiation on
TRAIL/Apo2L-mediated apoptosis in malignant glioma Emilio Ciusani, Danilo Croci,
Maurizio Gelati, Chiara Calatozzolo,
Francesca Sciacca, Luisa Fumagalli,
Marco Balzarotti, Laura Fariselli,
Amerigo Boiardi and Andrea Salmaggi
Department of Clinical
Investigation [E.C., D.C., M.B.], Department of Radiotherapy [L.Fu.,
L.Fa.], Department of Neurooncology [M.G., C.C., F.S., A.B., A.S.], National Neurological Institute  C.
Besta ,
Via Celoria, 11, Milan, Italy, 20133.
Correspondence to: Emilio Ciusani, Email: eciusani@istituto-besta.it,
Phone: +39-02-2394247, Fax: +39-02-2394535
The survival of patients with malignant gliomas is still
unsatisfactory despite multimodality treatment, therefore new
therapeutic strategies are required.
Tumor necrosis factor apoptosis
related ligand (TRAIL/Apo2L), a member of the tumor necrosis factor
superfamily, may induce apoptotic cell death in several tumors, but
not in normal cells, upon binding with specific receptors.
In the
present study, the expression and function of TRAIL receptors
(TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human
glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo
tumors and in primary cultures obtained from the tumors.
Our data show
that gliomas preferentially express TRAIL R2 and that treatment with
topotecan, a topoisomerase I inhibitor, significantly up-regulates its
expression as detected by flow cytometry and western blotting.
Moreover, in most cases, treatment with topotecan resulted in an
increased sensitivity to TRAIL-dependent apoptosis, although
cyclohexymide had to be added to induce apoptosis.
On glioma cell
lines, the effects of irradiation on TRAIL receptors were also
analysed.
In our experimental conditions, irradiation with 2 Gy
had a modest additive effect on TRAIL-dependent apoptosis and was not
able to modulate TRAIL receptor expression.
Keywords: apoptosis - glioma - radiation - topotecan - TRAIL
© Springer 2005
Source: http://springerlink.metapress.com/openurl.asp?genre=article&eissn=1573-7373&volume=71&issue=1&spage=19
DOI: http://dx.doi.org/10.1007/s11060-004-9180-4
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