Anti-tumor effect and mechanism analysis of arsenic trioxide on the subcutaneously transplanted tumor of human gastric carcinoma in nude mice

AIM: To study the effect and mechanism of arsenic trioxide (As203 ) at different concentrations on human gastric SCG-7901 cells implanted under the skin of nude mice in vivo, as well as the related toxicity. METHODS: The subcutaneously transplanted tumor models of human gastric carcinoma in nude mice were established and then were divided at random into 5 groups:1.0, 2.5 and 5.0 mg/kg As203,saline and 5-FU (20 mg/kg), each of which was composed of 5 nude mice and then received intraperitoneal injection in the following 10 d. The tumor inhibition rate was calculated and the gene expression of caspase-3 was detected by the real-time RT-PCR. The weight detection of pre- and post-administration, blood routine examination and hepatic and nephritic functional examination were carried out to evaluate the side effects of As203. RESULTS: 1.0 mg/kg As203 and 5-FU could obviously inhibit the growth of transplanted tumor with the tumor inhibitory rate of 60.6% and 78.2%, respectively; in contrast to the saline group, the differences were significant (P0.05). No significant difference was found in tumor inhibition rates among 2.5, 5.0 mg/kg As203 groups, 5-Fu group and saline group (P0.05). As203 showed the less haematological toxicity than 5-FU, and without hepatic and nephritic toxicity. The expression of caspase-3 was up-regulated obviously in the 1.0 mg/kg As203 group in contrast to the saline group with the statistic difference(P0.05). However, the expression of caspase-3 showed no difference among the groups of 2.5 mg/kg, 5.0 mg/kg and saline(P0.05). CONCLUSION: As203 at the concentration of 1.0 mg/kg could obviously inhibit the growth of the subcutaneous transplanted tumor of human grastric carcinoma in nude mice by up-regulating the expression of caspase-3 with the moderate white blood cell inhibition and without the hepatic and nephritic toxicity.