Studies On Effects Of Immunotherapy With BCG Liposome On Liver Tumor In Rats

Objective: To determine the effect on hepatocellular carcinoma of rats after the treatment of vein therapy with BCG liposome; to compare the effect and toxicity of vein therapy with BCG liposome or BCG in rats implanted liver tumor; to prepare for clinical application of BCG liposome.Methods: With the immediate injection method, a transplanted hepatoma model was made in SD rats by directly injecting Walker-256 cells into the lateral lobe of the liver. 60 male SD-rats were enrolled into this study. Half of them were randomized into three groups, each group contained 10 rats .Group A received treatment of vein therapy with BCG liposome, group B received treatment of vein therapy with BCG and group C , that is normal control group, received treatment of vein therapy with normal saline (N.S), respectively. One day after the last treatment, all rats were killed; every group's tumor volume and apoptosis ratio were determined and compared with each other, and average suppressed tumor ratios of group A and group B were calculated ; serum cytokines TNF-αexpression level was measured using immune kits and the levels of serum AST,ALT and TBIL were also investigated. The others were randomized into three groups and received treatment like before, to determine the survival time of every rat, to calculate the life prolonging rates of group A and group B and to make a survival analysis. And temperature and other physiological changes of every rat were detected to compare the toxicity of BCG liposome or BCG to rats.Results: After the treatment, the average suppressed tumor ratio was 60.14% in group A and was 42.46% in group B, respectively(p < 0.05).Tumor volume of group A and group B showed a significant reduction after treatment versus group C, respectively(p<0.01). The mean apoptosis ratio was 31.53% in group A, was 14.81% in group B, and was 3.27% in group C, respectively. Results of group A and B showed a significant elevation versus group C, respectively(p<0.05). It also showed a significant difference between group A and group B (P<0.05). TNF-αlevels of group A and group B were higher than group C (P<0.05), and level of group A was also higher than group B (P<0.05). Compared with normal saline group, administration of BCG liposome lowered the levels of AST and ALT in serum(P<0.05), while administration of BCG elevated the levels of AST and ALT in serum(P<0.05); but both of them had no effect on the amount of serum TBIL (p>0.05) . After vein therapy, the longest survival time was 26d that came from group A, while the shortest survival time was 6d that came from group C. Compared with group C, the life prolonging rates of group A and group B were 90.42% and 29.79%, respectively. There was significant difference about survival time between group A, group B and group C (p<0.05) .Temperature: results after treatment showed elevation versus the ones before treatment in both group A and group B, while there was no significant difference in group C (p>0.05) .It showed a significant difference between group A and group B after therapy (p< 0.01). It was same as group A versus group C. So was it between group B and group C (p<0.01) .Conclusions: Vein therapy with BCG liposome is able to inhibit the proliferation of liver tumor and promote apoptosis of hepatocellular carcinoma in rats; BCG liposome can prolong the survival time of rats implanted liver tumor much longer than BCG. The effect of BCG liposome is better than BCG, while damage to rats with liver tumor is weaker than BCG.