三氧化二砷抑制人胆囊癌裸鼠移植瘤生长及促凋亡作用

Arsenic trioxide inhibits the growth of transplanted tumor of human gallbladder carcinoma and promotes its apoptosis in nude mice

背景与目的:胆囊癌由于缺乏特异性的临床表现确诊时多属晚期,手术切除率较低,且常规化疗药物对胆囊癌的疗效较差,因此需寻找治疗胆囊癌新的有效药物。三氧化二砷(As2O3)在治疗急性早幼粒细胞白血病中取得了突破性成果,近年来它在实体瘤的研究中颇受关注。本研究旨在观察As2O3对人胆囊癌裸鼠移植瘤生长的抑制及促凋亡作用。方法:20只皮下接种移植瘤大小相似的BALB/c裸鼠,随机分为生理盐水(NS)组(n=10)和As2O3组(n=10)。尾静脉注射NS0.2ml/只(NS组)或As2O310mg/kg(As2O3组),每日1次,连续7d。21d时处死所有裸鼠,测量肿瘤的重量和体积,同时用原位末端标记法检测凋亡细胞并计数。结果:NS组瘤重(1.0±0.4)g、体积(1.5±0.6)mm3;As2O3组瘤重(0.53±0.27)g、体积(0.8±0.4)mm3,瘤重和体积明显下降;NS组凋亡细胞计数为22±4,As2O3组升高至58±10(P<0.01)。结论:As2O3能明显抑制人胆囊癌裸鼠移植瘤的生长并促进肿瘤细胞凋亡。

Background and purpose：Gallbladder carcinoma, lacking specific clinical manifestation, is usually diagnosed at advanced stages of the diseases and fewer can be resected in operation. Chemotherapy has not shown significant activity in gallbladder carcinoma, so new agents should be applied to its treatment. Arsenic trioxide, verified as a breakthrough in the management of acute promyelocytic leukemia, has been applied to the research of a variety of solid tumors. This study is to observe the inhibitory effect of As2O3 on the growth of transplanted tumor of human gallbladder carcinoma and its promotion on apoptosis in nude mice. Methods：20 BALB/c nude mice, with the similar volume of subcutaneous transplanted tumor, were randomly divided into normal saline（NS） and As2O3 groups. 0.2 ml NS or As2O3 10 mg/kg was injected into the tail vein of every mouse in NS group or As2O3 group, once everyday, for seven days. All mice were put to death fourteen days after the perfusion was completed, then the weight and dimension were assayed as well as the apoptotic cells were determined by TdT-mediated dUTP Nick-end Labeling（TUNEL）and counted.Results：The weight and volume of transplanted tumor was （1.0±0.4）g and （1.5±0.6）mm3 in NS group, which reduced to （0.53±0.27）g and （0.8±0.4）mm3 in As2O3 group. The apoptotic cells were 22±4 in NS group,which elevated uo 58±10 in As2O3 group. All the difference were significantly.Conclusions：As2O3 can significantly inhibit the growth of transplanted tumor of human gallbladder carcinoma and promote its apoptosis in nude mice.