Li Qi, Kan Xiaoxi, Yin Jie, Sun Lidong, Wang Yajie, Li Yujie, Yang Qing, Xiao Hongbin, Chen Ying, Weng Xiaogang, Cai Weiyan, Zhu Xiaoxin
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Front Pharmacol. 2018 Jan 22;8:963. doi: 10.3389/fphar.2017.00963. eCollection 2017.
The neovascularization functions essentially for malignant upgrading and predicts poor prognosis in multiple cancers, which make it the highly effective strategy for clinical treatment. Unfortunately, the known anti-angiogenic therapies show low effectiveness against breast cancer. Recently, rebalancing the pro-angiogenic property in microenvironment shows great advantages and attracts increasing attention for breast cancer treatment. Herein, we for the first time reported that Chamaejasmine B (ICJ), extracted from L., possessed potent anti-angiogenic effect in breast cancer. By Transwell, tube formation and aortic-ring assays, ICJ efficiently suppressed the neovascularization potential in tumor-HUVEC co-culture model. In Matrigel plug assay, the efficacy of ICJ was further identified . Mechanistically, with little influence on HUVEC apoptosis, ICJ obviously induced autophagy as proved by the elevated LC3I/II ratio, dotted distribution of LC3 and upregulated Beclin-1. Moreover, by associating with LC3 and in turn, inhibiting the level of VEGFR2, the anti-angiogenesis efficacy was closely dependent on the initiation of autophagy. Above results proved that, by attenuating the pro-angiogenic communication through VEGFR2, ICJ is a novel angiogenic inhibitor and will be a promising supplement for anti-angiogenic chemotherapy for breast cancer.
新生血管形成在本质上对恶性肿瘤进展起作用，并预示多种癌症的预后不良，这使其成为临床治疗的高效策略。不幸的是，已知的抗血管生成疗法对乳腺癌疗效不佳。最近，重新平衡微环境中的促血管生成特性显示出巨大优势，并在乳腺癌治疗中吸引了越来越多的关注。在此，我们首次报道从 中提取的蛇床子素B（ICJ）在乳腺癌中具有强大的抗血管生成作用。通过Transwell、管腔形成和主动脉环实验，ICJ有效抑制了肿瘤 - 人脐静脉内皮细胞（HUVEC）共培养模型中的新生血管形成潜能。在基质胶栓实验中，ICJ的疗效得到进一步确认。机制上，在对HUVEC凋亡影响较小的情况下，ICJ明显诱导自噬，这通过升高的LC3I/II比值、LC3的点状分布和上调的Beclin - 1得以证明。此外，通过与LC3结合进而抑制血管内皮生长因子受体2（VEGFR2）的水平，抗血管生成疗效紧密依赖于自噬的启动。上述结果证明，通过减弱经由VEGFR2的促血管生成信号传导，ICJ是一种新型血管生成抑制剂，将有望成为乳腺癌抗血管生成化疗的补充药物。
