C₃H마우스 섬유육종에 있어서 2-Deoxy-D-Glucose가 방사선 효과에 미치는 영향 : ³¹P-자기 공명 분광기와 유세포 분석기를 이용한 연구

Abstract

Since 2-Deoxy-D-Glucose(2-DDG) inhibits the glycolysis and malignant tumors have high rates of glycolysis, the potential anticancer effect of 2-DDG has been questioned. In this study, we evaluated the effect of 2-DDG on radiation response in a tumor by the growth delay assay and attempted to characterize the metabolic response and 2-DDG effects on cell cycle and proliferative capacity by means of in vivo ³¹P-MRS and flow cytomety, respectively. 3 dimensions of tumor were measured everyday and volume was calculated from the formula πABC/6. 120 amimals were evenly divided for 12 treatment groups; irradiated with 0Gy, 20Gy, 30Gy, 40Gy, 50Gy, and 60Gy in a single fraction with/without 2-DDG, 1gm/kg which was injected IP 1 day prior to irradiation. ³¹P-MRS were obtained on 4th-12th day after irradiation and averaged peak area of inorganic phosphate(Pi), phosphocreatine(PCr), phosphomonoester(PME) and β-ATP from the tumor of different treatment groups were compared. After 2-DDG injection, growth rate of tumor slowed down. Tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. In vivo ³¹P-MRS suggested that the rate of increase in PME and Pi by increasing size of tumor, slowed down after 2-DDG injection. Authors observed in irradiated group that 2-DDG slowed the rates of change in the ratio of Pi/βATP plotted as a function of days after the treatment but 2-DDG did not affect the rates of changes in PCr and PME. Flow cytometry showed significantly increased S-phase and G2 + M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG but authors did not observe any significant change in cell cycle fraction for irradiated group in the presnece of 2-DDG. Growth curves did not show any enhanced growth dealy by the addition of 2-DDG compared with that by radiation alone. Even though authors failed to observe any radiosensitizing effect of 2-DDG in this study, we felt that the findings from ³¹P-MRS were intriguing enough to warrant the further study with higher dose and different schedule of 2-DDG and radiation.

Since 2-Deoxy-D-Glucose(2-DDG) inhibits the glycolysis and malignant tumors have high rates of glycolysis, the potential anticancer effect of 2-DDG has been questioned. In this study, we evaluated the effect of 2-DDG on radiation response in a tumor by the growth delay assay and attempted to characterize the metabolic response and 2-DDG effects on cell cycle and proliferative capacity by means of in vivo ³¹P-MRS and flow cytomety, respectively. 3 dimensions of tumor were measured everyday and volume was calculated from the formula πABC/6. 120 amimals were evenly divided for 12 treatment groups; irradiated with 0Gy, 20Gy, 30Gy, 40Gy, 50Gy, and 60Gy in a single fraction with/without 2-DDG, 1gm/kg which was injected IP 1 day prior to irradiation. ³¹P-MRS were obtained on 4th-12th day after irradiation and averaged peak area of inorganic phosphate(Pi), phosphocreatine(PCr), phosphomonoester(PME) and β-ATP from the tumor of different treatment groups were compared. After 2-DDG injection, growth rate of tumor slowed down. Tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. In vivo ³¹P-MRS suggested that the rate of increase in PME and Pi by increasing size of tumor, slowed down after 2-DDG injection. Authors observed in irradiated group that 2-DDG slowed the rates of change in the ratio of Pi/βATP plotted as a function of days after the treatment but 2-DDG did not affect the rates of changes in PCr and PME. Flow cytometry showed significantly increased S-phase and G2 + M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG but authors did not observe any significant change in cell cycle fraction for irradiated group in the presnece of 2-DDG. Growth curves did not show any enhanced growth dealy by the addition of 2-DDG compared with that by radiation alone. Even though authors failed to observe any radiosensitizing effect of 2-DDG in this study, we felt that the findings from ³¹P-MRS were intriguing enough to warrant the further study with higher dose and different schedule of 2-DDG and radiation.