Liu Chia-Yuan, Liao Hui-Fen, Shih Shou-Chuan, Lin Shee-Chan, Chang Wen-Hsiung, Chu Cheng-Hsin, Wang Tsang-En, Chen Yu-Jen
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 104, Taiwan, China.
World J Gastroenterol. 2005 Jul 21;11(27):4237-40. doi: 10.3748/wjg.v11.i27.4237.
We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells.
Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0, 1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis.
Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively. G(2)/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL) nor with any dose after only 1 h of treatment.
Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment. Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G(2)/M arrest. Further study is necessary to elucidate the mechanism.
我们研究了秋水仙碱联合辐射对人肝癌HA22T/VGH细胞存活的影响。
用0 - 8 ng/mL秋水仙碱处理HA22T/VGH细胞24小时后,给予不同剂量(0、1、2、4和8 Gy)的辐射。进行集落分析以评估存活细胞分数。使用线性二次模型拟合存活曲线以估计增敏剂增强比(SER)。采用流式细胞术进行细胞周期分析。
较低浓度(1和2 ng/mL)的秋水仙碱与辐射具有明显的协同作用以抑制肝癌细胞生长,而较高浓度(4和8 ng/mL)与辐射仅具有相加作用。用1和2 ng/mL秋水仙碱预处理24小时可增强辐射对细胞的杀伤作用,SER分别为1.21和1.53。仅在24小时处理后用较高剂量(8和16 ng/mL)的秋水仙碱才观察到G(2)/M期阻滞;较低剂量(1、2和4 ng/mL)处理时未观察到这种效应,处理1小时后任何剂量处理均未观察到这种效应。
我们的结果表明秋水仙碱有潜力作为肝癌治疗放疗的辅助药物。较低剂量的秋水仙碱通过G(2)/M期阻滞以外的某些机制具有放射增敏作用。有必要进一步研究以阐明其机制。