三氧化二砷抑制人卵巢癌裸鼠腹腔转移瘤的形成及其机制的初步研究  

Primary Study of Arsenic Trioxide Inhibits Abdomino-MetastaticTumor Formation of Human Ovarian Carcinomain Nude Mice and Its Mechanisms

作　　者：黄守国[1] 孔北华[1] 杨瑞芳[1] 江森[1] 

机构地区：[1]山东大学齐鲁医院妇产科,山东济南250012

出　　处：《癌症》2002年第4期401-404,共4页Chinese Journal of Cancer

摘　　要：背景与目的:三氧化二砷(arsenictrioxide,As2O3)已成功地应用于急性早幼粒细胞白血病的临床化疗,并已用于治疗肝癌、结肠癌、胃癌等的实验研究。本研究探讨As2O3对人卵巢癌细胞株3AO细胞裸鼠腹腔种植转移的影响及其作用机制。方法:采用四甲基偶氮唑蓝(methylthiazolyltetrazolium,MTT)法检测不同浓度As2O3作用48h对人卵巢癌细胞株3AO细胞的生长抑制率,并与顺铂(cisplatin,cDDP)进行比较。取4×106个3AO细胞接种于裸鼠腹腔,96h后随机分为5组,分别腹腔内注射生理盐水、3mg/kg顺铂及0.8、1.2、2.4mg/kgAs2O3,观察3AO细胞在各组裸鼠的成瘤率、裸鼠的死亡率及生存期;采用流式细胞术观察As2O3作用后3AO细胞中Fas、FasL、nm23基因表达的变化。结果:As2O3能明显抑制3AO细胞的生长,抑制作用呈浓度依赖性,与顺铂相比差异有显著性(P<0.05);As2O3能明显降低3AO细胞的裸鼠成瘤率及荷瘤鼠的死亡率,延长荷瘤鼠的生存期,与顺铂相比差异有显著性(P<0.05);As2O3使裸鼠腹腔种植瘤Fas基因及nm23基因的表达水平升高(P<0.05),而对FasL基因的表达无影响(P>0.05)。结论:As2O3对人卵巢癌裸鼠腹腔种植具有明显的抑制作用,其机制可能与Fas基因及nm23基因的过度表达有关。Background and Objective:Arsenic trioxide (As2O3) has been successfully used to treat the patients with acute promyelocyutic leukemia in clinic, and for the experimental studies of liver cancer, colorectal cancer , gastric cancer, etc. The objective of this study was to explore the inhibitory effect of As2O3 on the abdomino metastasis of human ovarian carcinoma in nude mice and its mechanisms. Methods: Compared with cisplatin(cDDP), the growth inhibiting rates to human ovarian cancer cell line 3AO by treatment with various concentrations of As2O3 for 48 h were determined by methyl thiazolyl tetrazolium(MTT) method. After implanted with 3AO cells 4×106 into abdominal cavity for 96h, the nude mice were randomly divided into 5 groups and treated by intraperitoneal injection of normal saline, cisplatin, or different concentrations of As2O3. The rate of tumor formation, death rate, and survival period of tumor bearing nude mice were evaluated. After treatment with As2O3, the changes of Fas, FasL, and nm23 gene expressions were estimated by flow cytometry (FCM). Results: Compared with cisplatin, 3AO cell growth inhibiting rates by As2O3 were different significantly in concentration dependent manner (P< 0.05); Compared with cisplatin, As2O3 could reduce the 3AO cell tumor formation rate in nude mice and the death rate of tumor bearing nude mice, and prolong the survival period of tumor bearing nude mice significantly (P< 0.05). As2O3 up regulated Fas and nm23 gene expressions of abdominal cavity implanted tumors (P< 0 05), but did not affect FasL gene expression (P >0.05). Conclusion:As2O3 could inhibit the abdomino plantation of human ovarian carcinoma in nude mice and its mechanism may be associated with Fas gene and nm23 gene over expressions.

关 键 词：三氧化二砷 卵巢肿瘤 肿瘤种植 裸鼠 

分 类 号：R737.31[医药卫生—肿瘤]