As_2O_3对人卵巢癌顺铂耐药细胞株裸鼠腹腔移植瘤作用及其机制的探讨  

Effects and mechanisms of arsenic trioxide on abdomino-graft tumor of human ovarian carcinoma with cisplatin-resistant cell in nude mice

作　　者：黄守国[1] 陈瑾[1] 程虹[1] 陈芳[1] 吴清萍[1] 

机构地区：[1]中南大学湘雅海口医院妇产科,海南海口570208

出　　处：《中华肿瘤防治杂志》2010年第11期827-830,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：海南省自然科学基金[琼科(2008)30867]

摘　　要：目的:探讨三氧化二砷(As2O3)对人卵巢癌顺铂耐药细胞株3AO/DDP细胞裸鼠腹腔移植瘤的影响及其作用机制。方法:4×106个3AO/DDP细胞接种于裸鼠腹腔96 h后,随机分为5组,分别腹腔内注射0.2 mL生理盐水、3 mg/kg的DDP及0.8、1.2和2.4 mg/kg的As2O3,观察3AO/DDP细胞在各组裸鼠的致瘤率、裸鼠的死亡率及生存期;采用RT-PCR技术观察As2O3作用停药后1 d、1周、2周裸鼠腹腔移植瘤Fas、N-myc、nm23 H1及MTA1基因表达的变化,并与对照组相比较。结果:As2O3组裸鼠的致瘤率分别为87.5%、62.5%和50.0%,死亡率分别为62.5%、12.5%和0,生存期分别为(75.88±14.21)、(88.88±3.18)和(90.00±0.00)d,与DDP组的100%(致瘤率)、100%(死亡率)、(28.25±2.25)d(生存期)相比,差异有统计学意义,P<0.05;As2O3作用后,裸鼠腹腔移植瘤Fas及nm23 H1基因的表达水平升高,于停药第2周达到高峰,分别与对照组相比,差异均有统计学意义,P值均<0.05;N-myc和MTA1基因的表达在停药第1天和第1周下降,与对照组相比,差异有统计学意义(P<0.05),而第2周反弹升高,与对照组相比,差异无统计学意义,P>0.05。结论:As2O3对人卵巢癌裸鼠腹腔移植瘤具有明显的抑制作用,其机制与Fas和nm23 H1基因与N-myc和MTA1基因的正负调节有关。OBJECTIVE： To explore the effects and mechanisms of Arsenic trioxide（As2O3） on the abdomino-graft tumor of human ovarian carcinoma with cisplatin-resistant cell strain 3AO/DDP cells in nude mice.METHODS： Nude mice were planted with 3AO/DDP cell 4×10^6 in abdominal cavity,then were divided into 5 groups at random in 96 h,treated by intraperitoneal injection of normal saline 0.2 mL,DDP 3 mg/kg and As2O3 with 0.8,1.2 and 2.4 mg/kg respectively.The rate of tumor formation,death rate and survival period of tumor-bearing nude mice were evaluated.After treated with As2O3 in 1 day,1 week and 2 weeks,the changes of Fas,N-myc,nm23H1 and MTA1 gene expression were estimated by RT-PCR,and the results were compared with control group.RESULTS： The rate of 3AO/DDP cell tumor formation in nude mice were 87.5%,62.5% and 50.0%;the death rate were 62.5%,12.5% and 0;and the survival period of tumor-bearing nude mice were（75.88±14.21）,（88.88±3.18） and（90.00±0.00） days respectively in As2O3 groups,all of them were significant（P〈0.05） when compared with 100%（tumor formation）,100%（death rate） and（28.25±2.25） days（survival period） in DDP groups.As2O3 up-regulated Fas and nm23H1 gene expression in the abdomino-graft tumor in nude mice（P〈0.05）,and down-regulated N-myc and MTA1 gene expression in 1 day and 1 week（P〈0.05）,N-myc and MTA1 gene were over expression in 2 week（P〉0.05）.CONCLUSION： As2O3 inhibites the abdomino-graft tumor of human ovarian carcinoma in nude mice and these may related to bidirectional regulative expression of Fas,nm23H1 gene and N-myc,MTA1.

关 键 词：卵巢肿瘤 砷剂 肿瘤移殖 抗药性 多药 裸鼠 

分 类 号：R737.31[医药卫生—肿瘤]