5-氟尿嘧啶單獨或併用遊離輻射治療人類結腸直腸癌細胞之效果

Purpose: In this study 5-fluorouracil (5FU), ionizing radiation or combination of both was applied on human colorectal adenocarcinoma cells (SW480) in order to establish a better therapeutic strategy for clinical use.
Materials and Methods: Log-phase SW480 cells were used for all experiments. For 5FU treatment alone, cells were treated with 0, 0.1, 0.5, 1-0, 1.5 and 2.0mM 5FU for 3 hours. For radiation treatment alone, cells were irradiated for 0, 1, 1.5, 2, 4 and 6Gy. For combined treatment, cells were treated with 0.2mM 5FU and graded radiation doses using concurrent treatments or different order of sequence. Surviving fractions of cells were assayed by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl-terazolium bromide (MTT) method. Activity of thymidylate synthase and intracellular glutathione contents were also measured.
Results: The surviving fractions of SW480 cells were about 40% after three-hour treatments of 0.5mM, 1mM or 2mM 5FU. The 50% inhibition concentration (IC50) obtained from survival curve is about 0.4mM. Pre-irradiation 0.2mM 5FU treatment, post-irradiation 0.2mM 5FU treatment, and concurrent treatment of 0.2mM 5FU and radiation all had synergistic effect. However, the concurrent treatment of 5FU and radiation was found with the highest killing effect among the three different combined treatments. After 1mM and 2mM 5FU treatments for three hours, contents of reduced glutathione were 6.2±1.5nmole/mg and 5,2±2.6nmole/mg, respectively, and were significantly reduced (p＜ 0.05) as compared to 12±0.4nmole/mg of the control group. Contents of oxidized glutathione were 29.6±5.5nmole/mg and 29.8±2.7nmole/mg, respectively, and were significantly increased (p＜0.05) as compared to 20.5±3.0 amok/mg of the control group. Also, activities of thymidylate synthase were reduced to 0.59 ± 0.04pmole/min/mg and 0.36±0.15pmole/min/mg, respectively, as compared to 2.7±0.76pmole/min/mg of the control group, p＜0.01.
Conclusions: Concurrently combined 5FU with ionizing radiation showed the highest killing effect on SW480 human colorectal carcinoma cells. Reduced glutathione was significantly decreased in 5W480 cells after 1mM and 2mM 5FU treatments for 3 hours. The finding that the treatment of low concentration (0.2mM) 5FLJ with low doses of ionizing radiation (1Gy, 1.5Gy and 2Gy) still showed synergistic killing effect may have feasible clinical application in fractionated radiotherapy combined with chemotherapy for human colorectal carcinoma.