Objective To explore the anti-tumor effect of polymer nano-platinum(Ⅳ) on the mice with orthotopic liver cancer as well as its inhibitory effect on the cell activity of liver cancer. Methods (1) One hundred mice were enrolled to develop the mouse model of orthotopic liver cancer, and 36 liver cancer mice with successful modeling were divided into polymer nano-platinum (Ⅳ) group and oxaliplatin(Ⅱ) group,with 18 mice in each group. The two groups were treated with corresponding drugs. After 1,3,6,9,12,24 hours of intervention,the mice were sacrificed in batches,and the contents of platinum drugs in heart,liver,spleen,lung and kidney of mice were determined by inductively coupled plasma optical emission spectrometry. ( 2 ) Fifty-four liver cancer mice with successful modeling were divided into blank control group,polymer nano-platinum(Ⅳ) group and oxaliplatin(Ⅱ) group,with 18 mice in each group. The intervention groups were given corresponding drugs, while the blank control group was given an equivalent volume of normal saline. The mice were sacrificed in batches on the 1st,3rd,5th,7th,9th and 11th day after intervention,respectively,and tumor tissues were taken to measure the tumor volume. (3) The HepG-2 cells of logarithmic phase were divided into blank control group,0. 1 μg/ml,1 μg/ml,10 μg/ml and 100 μg/ml oxaliplatin(Ⅱ) groups,and 0. 1 μg/ml,1 μg/ml,10 μg/ml and 100 μg/ml polymer nano-platinum(Ⅳ) groups. The intervention groups were given corresponding concentrations of oxaliplatin (Ⅱ) or polymer nano-platinum (Ⅳ) , while the blank control group was given an equivalent volume of medium. After 48 and 72 hours of further culture,the cell activity was detected by methyl thiazolyl tetrazolium assay respectively. Results (1) After one hour of intervention,the content of platinum drugs in the liver and kidney tissues of mice in the oxaliplatin(Ⅱ) group was at the highest level,and the content of platinum drugs in liver tissues decreased with the increasing intervention time;the content of platinum drugs in liver tissues in the polymer nano-platinum(Ⅳ) group remained at a stable level,and the content of platinum drugs in renal tissues decreased significantly after six hours of intervention compared to the content at one hour after intervention. (2) The liver tumors of mice in the blank control group grew rapidly over time. The liver tumors of mice grew slowly in the oxaliplatin(Ⅱ) group and polymer nano-platinum(Ⅳ) group,no obvious growth of tumor was seen after 11 days of intervention,and the tumor volume presented a decreasing trend in the polymer nanoplatinum(Ⅳ) group since the 3rd day of intervention. (3) The activity of HepG-2 cells was lower after 48 hours of intervention but was higher after 72 hours of intervention in the oxaliplatin(Ⅱ) group compared to the activity in the polymer nano-platinum(Ⅳ) group. Conclusion Polymer nano-platinum(Ⅳ) has better therapeutic effects on the mice with orthotopic liver cancer.%目的 探讨高分子纳米铂(Ⅳ)对原位肝癌小鼠的抗肿瘤效果及对肝癌细胞活性的抑制作用.方法 (1)对100只小鼠构建原位肝癌模型,选取36只造模成功的肝癌小鼠分为高分子纳米泊(Ⅳ)组和奥沙利铂(Ⅱ)组各18只,给予相应的药物干预,于干预1h、3h、6h、9h、12h、24h后,分批处死小鼠,采用电感耦合等离子体发射光谱法测定小鼠心、肝、脾、肺、肾器官内铂药含量;(2)取54只造模成功的肝癌小鼠分为空白对照组、高分子纳米铂(Ⅳ)组和奥沙利铂(Ⅱ)组各18只,干预组给予相应的药物干预,空白对照组给予等体积的生理盐水,分别于干预后第1、3、5、7、9、11天分批处死小鼠,取肿瘤组织并测量肿瘤体积;(3)将对数生长期的HepG-2细胞分为空白对照组、不同浓度奥沙利铂(Ⅱ)组(0.1μg/ml、1μg/ml、10μg/ml、100μg/ml)以及不同浓度高分子钠米铂(Ⅳ)组(0.1μg/ml、1μg/ml、10μg/ml、100μg/ml),干预组分别给予相应浓度的奥沙利铂(Ⅱ)与高分子纳米铂(Ⅳ)干预,空白对照组加入等体积的培养液,继续培养48 h、72 h后分别采用四甲基偶氮唑盐比色法检测细胞活性.结果 (1)干预1 h时,奥沙利铂(Ⅱ)组小鼠的肝及肾组织中铂药含量最高,随着干预时间的延长,奥沙利铂(Ⅱ)组小鼠的肝组织中铂药含量逐渐下降;高分子纳米铂(Ⅳ)组小鼠肝脏组织中的铂含量基本保持于一个稳定水平,干预6 h时肾组织中的铂含量较干预1 h时明显下降.(2)空白对照组小鼠的肝脏体积随时间延长而迅速增大,奥沙利铂(Ⅱ)组及高分子纳米铂(Ⅳ)组小鼠肝脏肿瘤增长缓慢,干预11天时肿瘤组织未见明显生长,且从第3天开始高分子纳米铂(Ⅳ)组小鼠的肿瘤体积有减小趋势.(3)干预48 h时,奥沙利铂(Ⅱ)组HepG-2细胞的活性低于高分子纳米铂(Ⅳ)组,但干预72 h时相反.结论 高分子纳米铂(Ⅳ)对原位肝癌小鼠有较好的治疗效果.
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