Publication: p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose
1
Issued Date
2009
Resource Type
Language
eng
Rights
Mahidol University
Bibliographic Citation
International Journal of Oncology. Vol.35, No.3 (2009), 609-615
Suggested Citation
Chompunoot Sinthepibulyakit, Grimes, Kritopher R., Domann, Frederick E., Fang Fang, Yong Xu, Wanida Ittarat, Daret K. St. Clair, Clair, William St. p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose. International Journal of Oncology. Vol.35, No.3 (2009), 609-615. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/2115
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose
Abstract
Metabolic change in cancer cells by preferential
production of energy through glycolysis is a well-documented
characteristic of cancer. However, whether inhibition of
glycolysis will enhance the efficacy of radiation therapy is a
matter of debate. In this study which uses lung cancer as the
model, we demonstrate that the improvement of radiotherapy
by 2-deoxy-D-glucose (2DG) is p53-dependent. Based on
clonogenic survival data, we show that p53-deficient lung
cancer cells (H358) are more sensitive to 2DG treatment
when compared to p53 wild-type lung cancer cells (A549).
The effective doses of 2DG at 0.5-surviving fraction of A549
and H358 are 17.25 and 4.61 mM, respectively. Importantly,
2DG exhibits a significant radiosensitization effect in A549
cells but not in H358 cells. Treatment with 2DG increases
radiation-induced p53 protein levels in A549 cells. siRNA
inhibition of p53 in A549 cells reduces the radiosensitization
effect of 2DG. Furthermore, ectopic expression of wild-type
p53 in H358 cells significantly enhances the radiosensitization
effect of 2DG as determined by colony formation assay. In
nude mice injected with A549 cells, treatment of 2DG
enhances the efficacy of radiation therapy. Together, these
results suggest that inhibition of glycolysis may only be
beneficial for radiation therapy of cancer expressing wildtype p53.