Publication: p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose
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2009-09-21
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17912423
10196439
10196439
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2-s2.0-70349153884
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Mahidol University
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SCOPUS
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International Journal of Oncology. Vol.35, No.3 (2009), 609-615
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Chompunoot Sinthupibulyakit, Kristopher R. Grimes, Frederick E. Domann, Yong Xu, Fang Fang, Wanida Ittarat, Daret K. St. Clair, William St. Clair 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. doi:10.3892/ijo_00000372 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/27141
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p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose
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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 wild-type p53.