The Anti-tumor Effects Of Arsenic Trioxide(As₂O₃) On The Subcutaneous Transplantable Tumor Of Human Gastric SGC-7901 Cell Line In Nude Mice And Its Mechanism

Objective To study the anti-tumor effect and its mechanism of arsenic trioxide atdifferent concentration on human gastric cell line SGC-7901 implanted under the skin ofnude mice in vivo, as well as the related toxicity.Methods The subcutaneous transplantable tumor model of human gastriccarcinoma in nude mice were established and then were divided at random into fivegroups:1.0mg/kg,2.5mg/kg,5.0mg/kg As2O3 groups,saline group and 5-FU group andthen received intraperitonal injection in the following ten days. The tumor inhibitionrate was calculated to evaluate the anti-tumor effect. The weight change of pre-andpost-administration, the blood routing examination and the hepatic and nephriticfunctional examination were made to observe the side effect of arsenic trioxide. Theapoptosis rate and the activation of caspase-3 were detected by the flow cytometer. Thegene expression of caspase-3 was detected by the real-time quantitative RT-PCR.Result 1.0mg/kg As2O3 and 5-FU could obviously inhibit the growth oftransplantable tumor with the tumor inhibitory rates of 48.1% and 71.3% respectively. Incontrast to the group of saline, the difference is significant (p＜0.05). As2O3 showed theless haematological toxicity than 5-FU, but no hepatic and nephritic toxicity. Theapoptotic peak and the activation of caspase-3 was observed in each As2O3 group with theapoptosis rate 18.32%,17.86%,21.89% respectively for the 1.0mg/kg,2.5mg/kg and5.0mg/kg. The expression of caspase-3 was improved obviously in the 1.0mg/kg As2O3group in contrast to the saline with the statistic difference. However, the expression ofcaspase-3 showed no difference among the groups of 2.5mg/kg and 5.0mg/kg and saline.Conclusion arsenic trioxide at the concentration of 1.0mg/kg could obviouslyinhibit the growth of the human gastric subcutaneous transplantable tumor in nude mice; which may be relative to apoptosis induced by arsenic trioxide that regulated up theactivity and the gene expression of caspase-3, which was one of the target of arsenictrioxide. Arsenic trioxide has no the hepatic and nephritic toxicity...