Abstract:

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 25μmol·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·L^-1 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.

Key words: cadmium chloride;metallothionein;hepatocarcinoma