|
BCNU Down-Regulates Anti-Apoptotic Proteins Bcl-xL and Bcl-2 in
Association with Cell Death in Oligodendroglioma-Derived Cells
Richard A. Lytle, Zhihong Jiang, Xiao Zheng, Keith M.
Rich
Department of Neurosurgery, Washington
University School of Medicine, St. Louis, MO, USA
Oligodendroglial differentiation in gliomas is associated with enhanced
sensitivity to chemotherapy.
Anti-apoptotic proteins, Bcl-xL and Bcl-2, are
over-expressed in early passage cell lines derived from glioblastomas.
Down-regulation of Bcl-xL and Bcl-2 with DNA antisense oligonucleotides promotes
cell death in glioblastoma cells.
Changes of expression of Bcl-xL and Bcl-2
after chemotherapy treatment have not been studied in glioma subtypes.
The
current experiments correlate decreased expression of both Bcl-xL and Bcl-2
after BCNU chemotherapy and cell death in two oligodendroglioma-derived cell
lines.
Expression of Bcl-2 family member proteins Bcl-xL, Bcl-2, and Bax were
assessed in glioma cells both before and after chemotherapy treatment.
Cell
survival was assessed with a crystal violet bioassay.
Levels of expression of
Bcl-2 and Bcl-xL were elevated in two early passage oligodendroglioma-derived
cell lines compared with a non-neoplastic glial cell line.
BCNU chemotherapy
markedly down-regulated expression of Bcl-xL and Bcl-2 proteins in both
oligodendroglioma-derived cell lines.
Changes in expression of Bcl-xL and Bcl-2
were associated with the increased sensitivity to chemotherapy.
There were no
changes noted in expression of Bax after BCNU treatment.
Modulation of
expression of the anti-apoptotic proteins, Bcl-xL and Bcl-2, in the two
oligodendroglioma-derived cell lines was associated with increased sensitivity
to BCNU chemotherapy.
Down-regulation of Bcl-xL and Bcl-2 resulted in reversal
of the ratio of Bax/Bcl-xL and Bax/Bcl-2 and enhanced cell death after treatment
with BCNU.
Mechanisms that control expression of the anti-apoptotic proteins
Bcl-xL and/or Bcl-2 may be effective targets in treatment strategies in patients
with malignant gliomas.
Keywords: apoptosis, brain tumors, cell death, chemotheropy, deamidation, gliomas
Copyright
©
2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/119/A/7/abstract.htm
|
