As_2O_3对ACC-2移植瘤作用的实验观察  

Effects of Arsenic Trioxide on ACC-2 Xenografts in Nude Mice

作　　者：张斌[1,2] 高丽[2] 徐旭光[2] 焦宇飞[3] 吕志勇[2] 郁雷[4] 

机构地区：[1]哈尔滨工业大学市政环境工程学院,黑龙江哈尔滨150090 [2]哈尔滨医科大学附属第二医院口腔颌面外科,黑龙江哈尔滨150086 [3]哈尔滨医科大学附属第二医院,黑龙江哈尔滨150086 [4]哈尔滨医科大学附属肿瘤医院腹外科,黑龙江哈尔滨150086

出　　处：《口腔颌面外科杂志》2010年第2期98-103,共6页Journal of Oral and Maxillofacial Surgery

摘　　要：目的:研究三氧化二砷(As_2O_3)对人腺样囊性癌ACC-2裸鼠移植瘤生长的抑制作用,探讨其抗肿瘤的作用机制。方法:通过MTT法在体外证明不同浓度As_2O_3不同时间内对ACC-2细胞的抑制作用。建立ACC-2裸鼠移植瘤模型,将28只荷瘤鼠随机分为4组:阴性对照组(生理盐水)、阳性对照组[5-Fu 10 mg/(kg·d)]、低剂量As_2O_3组[2.5 mg/(kg·d)]、高剂量As_2O_3组[5.0 mg/(kg·d)]。连续经腹腔注射用药10 d。测量肿瘤的体积和重量,采用HE染色光镜观察,免疫组织化学法检测Ki-67、Survivin的表达。结果:不同浓度As_2O_3作用不同时间对ACC-2细胞有明显抑制作用,呈时间剂量依赖关系。As_2O_3作用组移植瘤的体积、重量均低于两对照组,且高剂量As_2O_3组抑瘤作用最明显,瘤体积抑制率为47.45%,瘤重抑制率为49.76%(P<0.0001)。As_2O_3组抑制移植瘤内Ki-67的表达,降低细胞增殖指数(PI)与两对照组比较以及高、低剂量As_2O_3组之间比较差异均有显著性,但其对Survivin表达抑制作用不如5-Fu组明显。结论:As_2O_3对人腺样囊性癌ACC-2裸鼠移植瘤有明显抑制作用,与常规化疗药物5-Fu相比效果更明显,其作用机制可能与降低Ki-67表达来抑制肿瘤细胞增殖活性及下调Survivin表达有关。Objective： This study was to investigate the inhibitory effect of Arsenic Trioxide （As2O3） on salivary adenoid cystic carcinoma-2 （ACC-2） cell xenografts in nude mice. Methods： The inhibitory ratio of cell proliferation of As2O3 in different concentrations （1.0, 2.5, 5.0 μmol/L） and time （24, 48, 72 h） on ACC-2 cells was detected by MTF. The nude mice with ACC-2 cell xenografts were randomly distributed into four groups, control normal saline （NS）, 5-Fu group [10 mg/（kg.d）], low-dose group [As2O32.5 mg/（kg.d）], and high-dose group [As2O3 5.0 mg/（kg.d）]. 0.2 mL NS or drugs were given by intraperitoneal injection for 10 days. Tumor volume and weight were measured, the microstructure was observed by pathological slides, the expression of Ki-67 and Survivin were detected by immunohistochemistry. Results： ACC-2 cell viability after As2O3 treatment was markedly suppressed and exhibited a dose- and time-dependent patter. The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in As2O3 groups than in control groups, especially in the high-dose group. The inhibitory rates were 49.76% and 47.45% （P〈0.0001）. The expression level of Ki-67 was significantly lower in As2O3 groups than in control groups, but the expression level of Survivin was higher in As2O3 groups than in 5-Fu group. Conclusion： As2O3 has obvious inhibitory effects on growth of ACC-2 cell xenografts in nude mice, and supressed the expression of Ki-67 and Survivin. The therapeutic effect of As2O3 is better than 5-Fu.

关 键 词：三氧化二砷 腺样囊性癌 裸鼠 移植瘤 

分 类 号：R739.8[医药卫生—肿瘤]