三氧化二砷对615系小鼠皮下移植性胃癌的抗癌作用及机制研究  

Anti-tumor effect and mechanisms of arsenic trioxide on subcutaneously implanted gastric cancer in 615 in-breeding mice

作　　者：梁军[1] 战淑珺[1] 赵园园[1] 沈方臻[1] 姚如永[1] 丁爱萍[1] 尚庆军[1] 

机构地区：[1]青岛大学医学院附属医院肿瘤治疗研究中心,青岛266003

出　　处：《第二军医大学学报》2004年第8期858-861,共4页Academic Journal of Second Military Medical University

基　　金：国家中医药管理局立项课题(00-01LL13).

摘　　要：目的:观察不同剂量三氧化二砷(As2O3)对于实体型胃癌移植瘤615系小鼠模型的抑瘤及诱导凋亡作用。方法:40只615系小鼠皮下注射鼠前胃癌细胞株MFC建立移植瘤模型,然后随机分为5组,每组各8只。分别在腹腔内注射5-Fu、生理盐水及不同剂量的As2O3(1、2、4 mg·kg-1·d-1),给药8 d,末次给药24 h后计算抑瘤率,流式细胞术观察凋亡率,透射电镜观察凋亡细胞超微结构,免疫组化半定量分析凋亡调控基因Bcl-2、Bax的表达情况。结果:As2O3对移植瘤生长有明显抑制作用,表现为瘤细胞超微结构出现凋亡征象且凋亡率增加,以2 mg·kg-1·d-1组作用最明显;免疫组化显示As2O3作用下Bcl-2基因阳性细胞数降低,Bax阳性细胞数则上升。结论:As2O3主要是通过诱导细胞凋亡对荷胃癌鼠皮下移植瘤具有明显抑制作用。Objective:To study the anti-tumor and apoptosis-inducing effect of arsenic trioxide (As2O3) on solid stomach carcinoma in transplanted tumor 615 mice models. Methods: Forty 615 mice were inoculated with mouse fore-stomach carcinoma cell line (MFC) to build transplantaion tumor animal models. Mice were then randomly divided into 5-Fu, NS, and As2O3 groups of different concentrations (1 mg · kg-1 · d-1 ,2 mg · kg-1 · d-1, 4 mg · kg-1 · d-1) (n = 8). The drugs were given for 8 d and 24 h after final-administration, the tumor inhibition rate (TIR) was calculated,the apoptosis rate was determined by flow cytometry(FCM) , the ultramicrostructure of cells was observed with transmission electron microscope, and the expressions of apoptosis-regulated genes :Bcl-2 and Bax were determined by immunohistochemistry. Results: As2O3 significantly inhibited the growth of transplanted tumor,resulting in apoptotic ultramicrostructure and increased apoptosis rate, especially in 2 mg · kg-1 · d-1 group. Immunohistochemistry showed that As2O3 down-regulated Bcl-2 protein and up-regulated the expressions of Bax. Conclusion : As2O3 significantly inhibits the transplanted tumor growth in mice bearing stomach carcinoma, mainly through inducing cell apoptosis.

关 键 词：三氧化二砷 胃肿瘤 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]