Effects of As_2O_3 on Expression of NF-κB p65,Survivin and Caspase-3 in Human Breast Cancer
Xi Chen
Abstract
Xi Chen
Abstract
Objective To investigate the effects of As_2O_3 on expression of NF-κB p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As_2O_3 group (1.5 and 3.0 mg/kg concentrations). The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-κB p65, survivin and caspase-3 protein were measured with immunohistochemistry. Results The positive rates of NF-κB p65 and survivin expression were higher in the control group than those in the DDP group and the As_2O_3 groups, but that of caspase-3 was on the opposite way (P0.01). The positive rates of NF-κB p65 and survivin in As_2O_3 group were negatively related with the concentrations of As_2O_3 (P0.01), but that of caspase-3 was on the opposite way (P0.01). The expressions of NF-κB p65 and survivin protein were positively correlated with that of survivin mRNA, but any of them was negatively correlated with the expression of caspase-3 protein. Conclusion As_2O_3 inhibites survivin probably by inhibiting the activity of NF-κB p65 and subsequently activates caspase-3, which induces apoptosis of human breast infiltrating duct carcinoma cells and is in a dose-dependent manner.
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Objective To investigate the effects of As_2O_3 on expression of NF-κB p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As_2O_3 group (1.5 and 3.0 mg/kg concentrations). The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-κB p65, survivin and caspase-3 protein were measured with immunohistochemistry. Results The positive rates of NF-κB p65 and survivin expression were higher in the control group than those in the DDP group and the As_2O_3 groups, but that of caspase-3 was on the opposite way (P0.01). The positive rates of NF-κB p65 and survivin in As_2O_3 group were negatively related with the concentrations of As_2O_3 (P0.01), but that of caspase-3 was on the opposite way (P0.01). The expressions of NF-κB p65 and survivin protein were positively correlated with that of survivin mRNA, but any of them was negatively correlated with the expression of caspase-3 protein. Conclusion As_2O_3 inhibites survivin probably by inhibiting the activity of NF-κB p65 and subsequently activates caspase-3, which induces apoptosis of human breast infiltrating duct carcinoma cells and is in a dose-dependent manner.
Key concepts: Survivin, Apoptosis, Immunohistochemistry, Cancer research, In situ hybridization, NF-κB, Messenger RNA, Breast cancer