镉抑制肝细胞癌生长和转移及锌的保护作用实验研究

目的:研究氯化镉(cadmium chloride)和硫酸锌(zinc sulfate)对肝细胞癌生长和转移的抑制作用.方法:建立人肝细胞癌异位种植转移模型.将荷瘤裸鼠60只随机分成五组,每组12只.种植1 w后开始,分别自腹腔一次性注射生理盐水(对照组)、氯化镉(Cd组三个剂量:1.0 mg,2.0 mg,3.0 mg/kg)、氯化镉(3.0 mg/kg)与硫酸锌联合应用(Zn+Cd).种植后第8周末处死动物,测量种植处肿瘤重量、体积,观察癌细胞转移及腹水出现情况,用免疫组织化学染色法(immunohistochemistry,IHC)检测肝脏及肝癌组织金属硫蛋白(metallothionein,MT).结果:各组均成瘤,Zn+Cd组、Cd组(3.0 mg,2.0 mg,1.0 mg/kg)与对照组相比,裸鼠肿瘤生长差异有显著性(P<0.05);腹膜转移率分别为8.3%、9.1%、18.1%、36.4%和100%(P<0.05);IHC检测,Zn+Cd组荷瘤裸鼠肝脏组织的MT染色明显加深,肝癌组织MT染色无明显改变.结论:镉对肝细胞癌生长和转移有较强的抑制作用;应用镉剂治疗前预用锌对正常肝组织有保护作用.

Inhibition of growth and metastasis of human hepatocellular carcinoma by cadmium and the protective effect of zinc against it in a nude mouse xenograft model

Objective:To study the effects of cadmium chloride and zinc sulfate on the growth and metastasis of hepatocellular cacinoma in vivo.Methods:A nude mice xenograft model was established by subcutaneously injecting SMMC-7721 cells,a HHC cell line,in the right shoulder. Sixty male nude mice were randomized into control,Cd(3.0 mg,2.0 mg,1.0 mg/kg,once.ip,respectively) and Zn+Cd group,respectively. After eight weeks tumour weight,volumes,metastasis and ascites,IHC for MT expression were evaluated,respectively.Results:Compared with control,tumour growth was significantly inhibited in treatment group and the incidence of peritoneal metastases was significantly inhibited in nude mice treated respectively with Cd(1.0 mg,2.0 mg,3.0 mg/kg) and Zn+Cd group(100%,36.4%,18.0%,9.1% and 8.3%). MT immunochemistry straining of liver showed the stains was stronger in the group pretreated with Zn than that of control group,which indicated that the MT can be induced by Zinc in normal tissue but not in hepatic cancer tissue.Conclusion:Cd has strong inhibitory effect both on tumour growth and metastases of human hepatocellular carcinoma. Pretreatment with Zinc has protective effects on hepatic cells.