Research of the effects of arsenic trioxide combined with 5-fluorouracil on mice liver cancer cell line H_(22) subcutaneously implanted liver cancer in vivo

Objective To evaluate the effects of arsenic trioxide(As2O3) combined with 5-fluorouracil(5-FU) on mouse hepatocarcinoma H22 subcutaneously transplanted tumor and provide the theoretical and experimental evidence for improving the clinical effects,reducing toxicity and overcoming drug resistance in the treatment of hepatocellular carcinoma.Methods Treat hepatocarcinoma subcutaneously transplanted tumor in mice with As2O3 and 5-FU in vivo: hepatocarcinoma H22 subcutaneously transplanted tumor models were established in 24 mice which were divided into four groups based on the tumor volume with drug intervention: NS group,As2O3(0.2 mg/kg) group,5-FU(10 mg/kg) group and As2O3(0.2 mg/kg)+5-FU(10 mg/kg) group.The mice was executed in the next day after discontinuing 2 weeks continuous intraperitoneal drug injection and blood and tumor specimens were conserved.The tumor volume was separately measured and compared,the tumor pathomorphological change after hematoxylin-eosin staining and the proliferating cell nuclear antigen(PCNA) were observed in each group.The transplantation of end labeling(TUNEL method) was used to observe the tumor cell proliferation situation,calculate apoptosis rate and test hepatic and renal functions relevant biochemical indexes in mice.Results The tumor volumes in each group had significant difference(F=252.7,P 0.01).The average tumor volumes of the groups with drug intervention were significantly lower than that in NS group(P 0.01).At the same time,the average tumor volume of As2O3+5-FU group was significantly lower than those of groups with As2O3 or 5-FU alone(P0.01).The cellproliferation index in As2O3 group was significantly lower than that in NS group(P0.05).The cell prolif-eration index in As2O3+5-FU group was significantly lower than those in NS group and As2O3group(P0.05),less than those in 5-FU group but no significant difference with it(P0.05).The apoptosis rate of the tumor in As2O3group was higher than that in NS group with statistical significance(P0.05).The apoptosis rate of thetumor in As2O3+5-FU group was significantly higher than those in As2O3 group and 5-FU group withstatistical significance(P0.05).The measurement values of serum ALT,AST,Cr in each groups had nosignificant difference(P0.05).Conclusion The combined application of As2O3 and 5-FU can significantlyenhance the inhibiting effect of mouse hepatocarcinoma subcutaneously transplanted tumor.Both of them had syner-gistic effect with the mechanism related to the enhancement on the inhibition of cell proliferation and induction of apoptosis.Also little side effects are found.