花青素抗HER-2阳性乳腺癌转移的效应及分子机制研究

HER-2阳性乳腺癌具有较强的转移能力是患者死亡的主要原因。前期研究证实，源于黑米的花青素提取物(BRACs)能抗HER-2阳性乳腺癌血管生成，而血管生成是肿瘤转移的前提条件。BRACs是否能抑制HER-2阳性乳腺癌的转移及其分子机制亟待探讨。本项目首先以HER-2阳性乳腺癌异种移植瘤为动物模型，在体探讨BRACs对HER-2阳性乳腺癌转移的抑制作用；然后以MDA-MB-435HAL为细胞模型，体外证实BRACs对HER-2阳性乳腺癌细胞的抑转移作用；最后利用免疫沉淀，荧光共聚焦，qRT-PCR等技术阐明BRACs通过阻断HER-2受体介导的FAK/Src/p130Cas、PI3K/AKT、Ras/ERK/MAPK、NF-κB/p65信号转导通路发挥抑制转移作用的分子机制。研究结果不但拓展了BRACs抗肿瘤转移的新生物学功能，而且为HER-2阳性乳腺癌的辅助治疗提供新的思路和作用靶点。

The potent metastasis capability of breast cancer overexpressing HER-2 is considered the main reason to cause patient　death. Our previous investigations have demonstrated that anthocyanidins-rich extract from black rice (BRACs) have potent anti-angiogenic effects in breast cancer overexpressing HER-2. The tumor angiogenesis is the prerequisite condition for metastasis. It is urgently need to further explore whether BRACs inhibit the metastasis of breast cancer overexpressing HER-2 and beyond the molecular mechanism. In the present research, first of all, we explore BRACs in vivo inhibit the tumor metastasis of breast cancer overexpressing HER-2 through xenotransplant tumor animal model. Thereafter, we further in vitro confirm BRACs inhibit the metastasis of breast cancer cells overexpressing HER-2 by MDA-MB-435HAL breat cancer cell model. At last, we elucidate the molecular mechanism of BRACs through inhibiting HER-2 receptor mediated FAK/Src/p130Cas、PI3K/AKT、Ras-ERK MAPK、NF-κB/p65 signal transduction pathways with immunoprecipitation, immunofluorescence confocal microscopy, and qRT-PCR molecular biologic techniques. The results of the present research not only expand the anti-tumor metastasis biological function for BRACs, but also provide a new hypothesis and some effective targets for preventing tumor metastasis of breast cancer overexpressing HER-2.