Experimental Studyof Arsenic Trioxide On Reduction Of Regulatory T Cells In Murine Colon Cancer Model With Pulmonarymetastasis

Objective: To explorethe impact of As2O3 on Tregsinfiltrated in the lung metastases of colon cancer andon the micro-environment of tumor.Methods: 1) High ratio of Tregs in pulmonary metastasis model of murine colon cancer was constructed by injection of CT26 through tail vein; 2) mice were divided into three groups: control group,injection of 200 ul/kg per mouce daily normal saline through tail vein; low doses group,injection of As2O33mg/kg per mouce daily through tail vein; high dose group,injection of As2O36mg/kg per mouce daily through tail vein; 3) Test the effects of As2O3 on the proportion of Tregs ofcytokine induced killer(CIKs)in vitro by flow cytometry, and estimate the level of activity of killing of CIKs in each group by LDH kits.Results: 1) Mice models of lung metastasis of colon cancer were established successfully, lung metastases were observed in three days and the rate of success was approach to 100%; the ratio of Tregs infiltrated in the lung metastasis of tumor-burden mice raised significantly compared with the normal ones by FACS 15 days later(p< 0.05); the ratio of Tregs in the peripheral blood had no significant differences between two groups(p>0.05); the ratio of Tregs in the spleen had significant differences(p< 0.05).2) experiment results in vivo:(1)both of the treatment groups could improve the body quality of the mice with pulmonary metastasis significantly(p<0.01) and there were significant differences between the two treatment groups(p<0.01); the number of pulmonary metastasis nodule in both of the As2O3 treatment groups were reduced significantly(p<0.01), however there were no significant difference between the two groups(p>0.05); the weigh of the lungs were also reduced significantly, no significant difference were observed between the two groups(p>0.05).(2) the ratio of Tregsinfiltrated in the lung metastasis in the treatment groups were declined significantly(p<0.01) and significant difference between the two groups were confirmedtoo(p<0.05);(3)the redistribution of lymphocytes in the tumor-burden mice were verified simutaneously, characterized by the details as followed:the proportion of T lymphocytes infiltrated in the lung metastasis of the treatment groups had raised significantly(p<0.01),raised in peripheral blood and the spleen(p<0.01), but no significant difference were observed between the two groups(p>0.05); 3) the proportion of Tregs in the CIKs dropped significantly by As2O3 in vitro(p<0.01) and significant differences were detected between groups(p<0.05),and the killing activity of CIKs in vitro had improved significantly(p<0.01) and significant differences were observed between each group(p< 0.01).Conclusions: As2O3 could not only reduce the proportion of Tregs of CIKs in vitro, but also improve the killing activity of CIKs. The immune mechanisms of As2O3anti-tumor effects might bevia reducing the proportion of Tregs and regulating the redistribution of lymphoid cells.