6 / 9
Page 42
Notes:
ISSN:2171-6625
http://www.jneuro.comSeptember 18-19, 2017 | Dallas, USA
4
th
International Conference on
NEUROLOGY AND NEUROIMMUNOLOGY
T
he current standard treatment of malignant gliomas
includes surgery, followed by Temozolomide (TMZ) -
Radiotherapy. It leads to increased survival as compared to
radiotherapy alone. However, haematological toxicities are
also increased by the combination treatments. Therefore,
it is important to carry out further preclinical studies,
to develop more effective treatment for these tumors.
2-Deoxy-D-Glucose (2-DG), an inhibitor of glycolytic energy
metabolism, has been shown earlier to differentially inhibit
repair processes, growth and survival of cancer cells. It has
been tolerated very well in combination with radiotherapy in
clinical trials on malignant gliomas. In the present study, we
investigated the effects of combination of clinically relevant
concentrations of 2-DG (0.5 mM and 1 mM) and TMZ (2
µM and 5 µM) ± Radiation (1Gy) on cell proliferation, total
cellular damage (TCD) and colony formation in an established
glioblastoma cell line (U251MG), and primary cultures
derived frommalignant glioma tumor pieces. The monolayer
cultures were grown on cover slips and stained with Acridine
Orange (0.002%) after drug treatments and irradiation,
for the study of cellular damage and death. Exponentially
growing cells were exposed to drugs and Gamma irradiation.
Drugs were removed 4 hrs after irradiation and cultures
were processed for different assays of cell death and
damage. Our results showed that combination of 2-DG with
TMZ±Radiation significantly inhibited the cell proliferation
up to 6 days. The TCD was significantly increased by the
combination of drugs in primary as well as in established cell
line. Cell proliferation as measured by MTT assay showed
that drugs ± radiation significantly reduced proliferation
response. Cell survival inhibition after combination of TMZ+2-
DG+Gamma (2µM+0.5mM+1Gy) showed more than additive
effects. These results suggest that targeting glycolytic energy
metabolism by agents such as 2-DG can enhance the efficacy
of TMZ+Radiation Therapy for malignant gliomas, without
increasing toxic side effects.
e:
kalyani.icmr@gmail.com kalyani.neuro@gmail.comPotential strategies to improve Temozolomide/radiation therapy of malignant gliomas by targeting
glycolytic energy metabolism
Kalyani Thakur
1
, Sai Shyam
2
and
Vijay Kumar Kalia
2
1
National Centre for Disease Informatics and Research (ICMR), India
2
National Institute of Mental Health and Neuro Sciences, India
J Neurol Neurosci, 8:5
DOI: 10.21767/2171-6625-C1-003