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題名 | 5-氟尿嘧啶單獨或併用游離輻射治療人類結腸直腸癌細胞之效果=Combined Treatment Effect of 5-Fluorouracil with Ionizing Radiation on Human Colorectal Carcinoma Cells |
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作者 | 黃正仲; 陳柏元; 鄧文炳; 黃家瑜; 林冠如; 吳國海; 傅秉三; 林芳仁; | 書刊名 | 放射治療與腫瘤學 |
卷期 | 6:2 1999.06[民88.06] |
頁次 | 頁73-82 |
分類號 | 416.245、416.245 |
關鍵詞 | 5-氟尿嘧啶; 人類結腸直腸癌SW480細胞; 游離輻射; 合併治療; 協同作用; 5-fluorouracil; Human colorectal adenocarcinoma SW480 cells; Ionizing radiation; Combined treatment; Synergistic effect; |
語文 | 中文(Chinese) |
英文摘要 | Purpose: In this study 5-fluorouracil (5FU), ionizing radiation or combination of both was applied or 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, O.1, 0.5, 1.0, 1.5 and 2.0 mM 5FU for 3 hours. For radiation treatment alone, cells were irradiated for 0, 1, 1.5,2,4 and 6 Gy. For combined treatment, cells were treated with 0.2 mM 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 0.4 mM. Pre-irradiation 0.2 mM 5FU treatment, post-irradiation 0.2 mM 5FU treatment, and concurrent treatment of 0.2 mM 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 1 mM and 2 mM 5FU treatments for three hours, contents of reduced glutathione were 6.2��1.5 nmole/mg and 5.2��2.6 nmole/mg, respectively, and were significantly reduced (p < 0.05) as compared to 12 ��0.4 nmole/mg of the control group. Contents of oxidized glutathione were 29.6 ��5.5 nmole/mg and 29.8��2.7 nmole/mg, respectively, and were significantly increased (p < 0.05) as compared to 20.5��3.0 nmole/mg of the control group. Also, activities of thymidylate synthase were reduced to 0.59 ��0.04 pmole/min/mg and 0.36�� 0.15 pmole/min/mg, respectively, as compared to 2.7��0.76 pmole/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 SW480 cells after 1 mM and 2 mM 5FU treatments for 3 hours. The finding that the treatment of low concentration (0.2 mM) 5FU with low doses of ionizing radiation (1 Gy, 1.5 Gy and 2 Gy) still showed synergistic killing effect may have feasible clinical application in fractionated radiotherapy combined with chemotherapy for human colorectal carcinoma. |
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