Arsenic Trioxide(AS_2O_3) Combined with Vitamin C(Vit C) Affect the Activity of Effect of arsenic trioxide(AS_2O_3) combined with Vitamin C on Caspase-3 and Survivin activiation in the subcutaneously transplanted tumor of drug resistant human lung carcinom

Objective To study the effect and mechanism of arsenic trioxide(AS2O3) combined with Vitamin C on the subcutaneously transplanted tumor of drug resistant human lung carcinoma in nude mice.Methods The subcutaneously transplanted tumor models of drug resistant human lung carcinoma in nude mice were established and then were divided into NS,Vit C(250 mg/kg),1.5,3 mg/kg AS2O3,and combining AS2O3 with Vit C groups.They were injected intraperitoneally two weeks.The weight of mice and volume of tumor pre-and post-administration were measured.All mice were killed after administration and the mass of tumor was measured and tumor inhibition was calculated.Immunohistochemical staining was used to observe the expressions of Caspase-3 and Survivin protein.RT-PCR and Western blot were used to detect the expressions of Caspase-3 and Survivin.Results The tumor inhibitory rate of Vit C,1.5,3 mg/kg AS2O3,and combining AS2O3 with Vit C were 3.47%,42.3%,66.25%,79.93%.The volume,mass of tumor were decreased after treatment.Compared with NS group,the differences were significant(P0.01).The tumor mass and volume were decreased in the test groups,and effects of the combined drug group was better than that of single-drug groups.Moderate necrosis was found in tumor tissues,and Caspase-3 protein positive rate was increased,Survivin protein positive rate reduced.The expressions of Survivin mRNA and protein in the combination group were markedly lower than those of the other groups and the expression of Caspase-3 mRNA was higher.Conclusions AS2O3 combined with Vit C has stronger inhibition effect on tumor growth than single use of one drug.AS2O3 and Vit C have a synergic anticancer effect on transplanted lung cancer in nude mice,which possible mechanism is related to down-regulation of the expression of Survivin and up-regulation of the expression of Caspase-3.Application of Vit C and AS2O3 might be a chemotherapy combination with low toxicity and efficient.