三氧化二砷-泊洛沙姆407缓释剂治疗裸鼠肝癌移植瘤的作用与机制

Effects and its mechanism of arsenic trioxide-poloxamer 407 on nude mice transplants of human hepatic carcinoma

目的:对比三氧化二砷(As2O3)-泊洛沙姆407缓释剂(As2O3-P407)与亚砷酸注射液(As2O3溶液)对裸鼠肝癌移植瘤的疗效并探讨可能机制。方法:以人肝癌HepG2细胞为来源建立裸鼠皮下移植瘤模型,实验共分3组,As2O3-P407缓释制剂治疗组(As2O3-P407组),As2O3治疗组(As2O3组)与生理盐水对照组(NS组),于造模后6～8天分别行瘤体注射每4天1次,4次为1个疗程。观察各组裸鼠治疗前后肿瘤体积变化及抑瘤率,各组裸鼠肿瘤组织分别行HE染色、TUNEL法检测、透射电镜观察,对比病理改变及肿瘤细胞的凋亡情况。结果:治疗后As2O3-P407组裸鼠肿瘤体积较As2O3组和NS组明显缩小(P<0.05);两治疗组抑瘤率分别为72%和46%;光镜下各治疗组肿瘤组织病理改变有意义;As2O3-P407组肿瘤细胞凋亡率明显高于As2O3组;电镜超微结构同样提示As2O3-P407组肿瘤凋亡细胞增加。结论:As2O3-P407缓释剂瘤内注射,可维持局部有效药物浓度、延长作用时间,疗效优于普通AsO注射液瘤内注射,其作用机制可能与增加肿瘤细胞凋亡有关。

Objective：To contrast the therapeutic effects of arsenic trioxide-poloxamer 407（As2O3-P407） and As2O3 on the human hepatic carcinoma cell（HepG2） subcutaneously implanted in nude mice and to investigate its mechanism.Methods：Nude mice were subcutaneously transplanted with human HepG2,and then divided into 3 groups.As2O3-P407 group,As2O3 group and physiological saline group.Intratumoral injection were carried out respectively 6～8 days after the nude mice model were established.Every four days one time,four times totally.The changes of tumor size and the inhibitory rate of tumor in each group were observed.The tumor tissue slices of each group were detected by HE dyeing,TUNEL detection and electron microscope to contrast the patho-changes and apoptosis of tumour cells.Results：The tumor growth of the As2O3-P407 treatment group were significantly inhibited;the size of the tumor was significant smaller than the As2O3 treatment group and NS control group（P0.05）;The inhibitory rate of humor about As2O3-P407 treatment group and As2O3 treatment group were 72% and 46%.The patho-changes of each group had significant difference through electron microscope.Apoptosis rate of tumour cells in As2O3-P407 treatment group were significantly increased than As2O3 treatment group.Ultrastructure under electron microscope also showed the apoptosis tumour cells in As2O3-P407 treatment group were significantly increased.Conclusion：As2O3-P407 through intratumoral injection can maintain the active concentration and prolonged the action time in the tumor foci.The curative effect of As2O3-P407 is better than ordinary As2O3 administration.It＇s mechanism of action may related to the apoptosis of tumour cells.