As2O3抑制肿瘤血管生成，但调控机制尚不明了。研究表明，核转录因子FoxO3a作为一种新的抑癌分子，调控肿瘤血管生成，在抑制乳腺癌发生发展中起到重要作用；而IKKβ可负性调节乳腺癌中FoxO3a活性。但IKKβ/FoxO3a是否参与乳腺癌血管生成的研究未见报道。本课题组前期研究发现As2O3可抑制IKKβ活性，提示As2O3可能通过抑制IKKβ使FoxO3a活性增加，阻断乳腺癌肿瘤血管生成，继而抑制乳腺癌生长。据此，本项目从整体动物、细胞和分子水平，以IKKβ/FoxO3a信号通路为切入点，运用慢病毒干扰、条件性基因剔除小鼠等技术，证实IKKβ/FoxO3a参与调控肿瘤血管生成，阐明As2O3基于IKKβ/FoxO3a的抑制肿瘤血管生成的分子机制，为IKKβ/FoxO3a作为抗乳腺癌领域的新的生物学标志和药物作用靶点提供科学依据，为As2O3在乳腺癌领域的临床应用提供理论依据和实验支持。

At present, the underlying mechanism of tumor angiogenesis inhibited by As2O3 remains unclear. Researches have indicated that the nuclear transcription factor FoxO3a as a new anti-oncogene can regulate tumor angiogenesis and perform a primary role in the inhibition of breast cancer development. The activity of FoxO3a in breast cancer can be negatively regulated by IKKβ, but whether or not IKKβ/FoxO3a contributes to the angiogenesis within breast cancer has not been reported yet. As2O3 can block the activity of IKKβ according to our previous studies. The results demonstrate that through inhibiting IKKβ, As2O3 may enhance the activity of FoxO3a and prevent the angiogenesis within breast cancer, to block breast cancer growth. Based on the above findings, this present study will investigate at whole animal, cellular and molecular levels with the IKKβ/FoxO3a signaling pathway at a starting point and adopt techniques including Lentiviral-mediated RNA interference and conditional gene knockout mouse models. This study is intended to confirm IKKβ/FOxO3a involvement in the regulation of tumor angiogenesis and explain the IKKβ/FoxO3a based molecular mechanism of As2O3 to inhibit tumor angiogensis. It will further provide scientific supporting for the role of IKKβ/FoxO3a as a new biological marker and pharmaceutical target in the anti-breast cancer field and theoretical and experimental evidence for the use of As2O3 in clinical anti-breast cancer treatment.