氯化镉对肝癌细胞增殖的抑制作用

目的：探讨氯化镉对肝癌细胞增殖的抑制作用，阐明氯化镉对正常组织与肿瘤组织作用效应差异的分子机制。方法：以5、10、25和50 μmol·L^-1氯化镉分别作用于人肝细胞癌细胞株HepG-2和SMMC-7721，6 h后应用MTT法检测细胞增殖；应用25μmol·L^-1氯化镉作用于肝癌细胞株，分别于3、6、12和24 h后检测细胞增殖。应用裸鼠建立荷人肝癌模型，以0.25、1.00及4.00 mg·kg^-1氯化镉及10 mg·kg^-1氯化锌联合1.0mg·kg^-1氯化镉腹腔注射荷瘤鼠，测定生存期及给药8周后肿瘤体积；采用免疫组织化学方法测定正常肝组织及肝癌组织中金属硫蛋白(MT)表达水平。结果：5、10、25及50μmol·L^-1氯化镉均可抑制HepG-2和SMMC-7721增殖，其细胞增殖抑制率高于对照组（P< 0.05），随着剂量和作用时间的增加，肿瘤细胞增殖抑制率增加；0.25、1.00及4.00 mg·kg^-1氯化镉及锌＋镉组肿瘤细胞体积较对照组明显减小（P< 0.05），生存期明显延长（P< 0.05），锌＋镉组与1 mg·kg^-1氯化镉组比较肿瘤体积差异无显著性，生存期延长（P< 0.05）。免疫组织化学结果显示，肿瘤组织中MT表达明显低于正常组织，正常肝组织预先应用氯化锌组MT表达水平高于正常组，而在肿瘤组织中表达无变化。结论：氯化镉具有显著的抗肝癌作用，在应用氯化镉前给予锌可以提高正常组织中MT表达水平而起到保护作用；在肝癌组织中MT表达减低，并不能被锌诱导增加。

Suppressing effect of cadmium chloride on proliferation of hepatocarcinoma

Objective To investigate the suppressing effect of cadmium chloride on proliferation of hepatocarcinoma,and to discuss the mechanism for the difference of cadmium chloride between normal and tumor tissue.Methods Hepatocarcinoma cell lines HepG-2 and SMMC-7721 were treated with 5,10,25 and 50 μmol·L-1 cadmium chloride for 6 h,MTT essay was used to measure the inhibition of proliferation of HepG-2 and SMMC-7721 cells;Instantaneously,HepG-2 and SMMC-7721 cells were treated with 25 μmol·L-1 cadmium chloride for different time,the inhibition of proliferation was also measured.Athymic mice were used to establish the human hepatocarcinoma animal models,the survival day and tumor volume 8 weeks after drug administration were detected;the metallothionein(MT) levels in normal and tumor tissues were determined by immunohistochemimal staining.Results Compared with control group,5,10,25 and 50 μmol·L1 cadmium chloride inhibited the proliferation of hepatocarcinoma cell lines(P< 0.05),the inhibitory rate increased with the dose of drug and action time.Compared with control,the tumor volumes in model mice were significantly decreased in 0.25,1.00 and 4.00 mg·kg-1cadmium chloride and ZnCl2+CdCl2 groups(P< 0.05) and the survival day increased(P< 0.05).The tumor volume in ZnCl2+CdCl2 group had no difference with 1 mg·kg-1 cadmium chloride group,however,the survival day was longer(P< 0.05).The result of immunohistochemical staining showed the MT level in hepatocarcinoma tissue was significantly lower than that in normal liver tissue,the MT level was increased significantly in normal liver tissue pretreated with ZnCl2,otherwise it was no change in hepatocarcinoma tissue.Conclusion Cadmium chloride has anti-tumor effect on hepatocarcinoma.Pretreatment with ZnCl2 could increase the MT level in normal liver tissue;the MT level in tumor tissue is lower and could not be induced by zinc.