地西他滨对人胆管癌CCLP1细胞增殖的影响  

The effect and mechanism of decitabine on the proliferation of human cholangiocarcinoma

作　　者：王兵[1] 杨锐[1] 李红波[1] 胡走肖[1] 吴越[1] 周顺长[1] 邹声泉[1] 

机构地区：[1]华中科技大学附属同济医院,武汉430030

出　　处：《中华肝胆外科杂志》2013年第11期852-856,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：国际科技合作项目基金（2010DFA31870）

摘　　要：目的探讨地西他滨（DAC）对人胆管癌CCLP1细胞增殖的影响及其可能的作用机制。方法采用CCK-8法检测细胞生长抑制率；应用流式细胞仪检测细胞周期变化及凋亡发生情况；荧光显微镜观察经DAC作用后细胞的自噬现象。体内试验采用裸鼠CCLP1细胞皮下种植瘤模型，观察DAC对瘤体生长的影响。结果DAC对人胆管癌CCLP1细胞的生长抑制作用呈剂量和时间依赖性（P〈0．05）。流式细胞术检测显示，随着药物浓度的增加，CCLP1细胞的细胞周期呈现明显的G2／M阻滞，且凋亡细胞明显增多。荧光显微镜下观察到，经250μmol／LDAC作用CCLP1细胞后，有明显的自噬现象发生。体内试验证明：当DAC腹腔注射剂量为0．8mg／kg时，每周给药6次，总给药时间为2周，对裸鼠CCLP1细胞皮下移植瘤的生长有明显的抑制作用。结论体内、外实验证明，DAC对胆管癌的生长有明显的抑制作用。Objective To investigate the effect and mechanism of decitabine （DAC） on the pro- liferation of human cholangiocarcinoma CCLP1 cells in vitro and in vivo. Methods After treated with various concentrations of DAC, cell growth inhibition rates were determined by CCK-8 assay. Cell cy- cle and cell apoptosis were analyzed by flow cytometry. Cell autophagy was observed under fluores- cence microscope. The effect of DAC on the growth of cholangiocarcinoma in vivo was determined in a CCLP1 mice xenograft model. Results The proliferation rate of CCLP1 cells in the DAC-treated group deereased in a time-concentrated dependent manner. After treatment with DAC, the cell cycle of CCLP1 cells was arrested at the G2/M phase. The apoptosis rate was significantly higher in the treat- ment group over the Control group. Cell autophagy was observed after treatment with DAC in CCLP1 cells. The tumor growth of implanted CCLP1 cells significantly slowed down after the mice were trea- ted with 0.8 mg/kg DAC, 6 times weekly for 2 weeks. Conclusion DAC can inhibit the proliferation of cholangiocarcinoma in vitro and in vivo.

关 键 词：地西他滨 胆管肿瘤 细胞增殖 肿瘤移植 

分 类 号：R735.8[医药卫生—肿瘤]