摘要
目的探讨去甲斑蝥素(norcantharidin,NCTD)对荷瘤裸鼠胆囊癌移植瘤增殖和凋亡的影响。方法建立裸鼠人胆囊癌种植瘤模型,实验分为对照组、5-FU组、NCTD组、NCTD+5-FU组4组。测定移植瘤大小、生长曲线和抑瘤率,应用流式细胞术、光学和电子显微镜观察移植瘤细胞的细胞周期、凋亡率和形态学改变。数据统计采用SPSS11·5软件包方差分析或χ2检验。结果NCTD对荷瘤鼠的半数致死量(LD50)为139·96mg·kg-1。应用1/5LD50即可使裸鼠移植瘤明显缩小(5·61±0·39vs.9·78±0·61cm3,P=0·000),抑瘤率增高(42·63%vs.0,P=0·012);移植瘤细胞周期中S期细胞明显减少(43·47%±2·83%vs.69·85%±1·96%,P=0·000),凋亡率上升(5·49%±0·59%vs.15·08%±1·49%,P=0·000);与5-FU合用时上述作用更明显(P=0·000)。NCTD作用后的移植瘤细胞经光镜检查见胞核固缩,核碎裂等现象;电镜显示典型的凋亡细胞及凋亡小体。结论NCTD可明显抑制荷瘤裸鼠胆囊癌移植瘤的增殖和生长,若与5-FU合用呈协同效应,可加强其抗癌作用。
Objective To explore the effect of norcantharidin (NCTD) on proliferation and apoptosis of implanted human gallbladder carcinoma in nude mice. Methods GBC-SD cells of human gallbladder carcinoma were implanted subcutaneously into nude mice. Mice were randomly divided into control, 5-FU, NCTD and NCTD + 5-FU -treatment groups. Tumor size, growth curve and inhibitory rate was respectively evaluated. Cell cycle and apoptosis were measured. Morphological changes of tumorous cells were observed. Results LD50 of NCTD for nude mice was 139.96 mg·kg^-1. Tumor volume (5.61±0.39 cm^3 vs. 9. 78 ± 0. 61 cm^3 , P=0.000) , percentage of the S phase cells (43.47%±2. 83% vs.69. 85%±1.96% , P =0.000) in NCTD group was smaller than that in control group, with tumor inhibitory rate (42.63% vs. 0, P=0.012) and cell apoptosis rate (5.49% ±0.59% vs. 15.08%±1.49%, P=0.000) being increased. Compared with other groups,the difference on tumor volume (4.51±1.11cm^3) ,tumor inhibitory rate (53.89%), percentage of the S phase cells (33.76%±2.39% ) and cell apoptosis rate (18.68%±2. 38%) in NCTD + 5-FU group was statistically significant (P=0.000) , with increased nuclear shrinkage, karyorrhexis and typical apoptosis. Conclusion NCTD inhibits the growth of implanted tumor of human gallbladder carcinoma in nude mice. The inhibitory effect could be intensified when combined with 5-FU.
出处
《中华普通外科杂志》
CSCD
北大核心
2005年第7期438-441,共4页
Chinese Journal of General Surgery
关键词
去甲斑蝥素
荷瘤裸鼠
胆囊癌
移植瘤增殖
细胞凋亡
消化系统
NCTD
Gallbladder neoplasms
Drug screening assays, antitumor
Proliferation
Apoptosis
Norcantharidin
Animal experiment