Gu Yuan, Körbel Christina, Scheuer Claudia, Nenicu Anca, Menger Michael D, Laschke Matthias W
Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar 66421, Germany.
Oncotarget. 2016 Feb 2;7(5):5258-72. doi: 10.18632/oncotarget.6676.
Tubeimoside-1 (TBMS1) is a potent anti-tumor phytochemical. Its functional and molecular mode of action, however, remains elusive so far. Since angiogenesis is essential for tumor progression and metastasis, we herein investigated the anti-angiogenic effects of the compound. In a non-small cell lung cancer (NSCLC) xenograft model we found that treatment of CD1 nu/nu mice with TBMS1 (5 mg/kg) significantly suppressed the growth and vascularization of NCI-H460 flank tumors. Moreover, TBMS1 dose-dependently reduced vascular sprouting in a rat aortic ring assay. In vitro, TBMS1 induced endothelial cell apoptosis without decreasing the viability of NSCLC tumor cells and inhibited the migration of endothelial cells by disturbing their actin filament organization. TBMS1 further stimulated the proteasomal degradation of vascular endothelial growth factor receptor-2 (VEGFR2) and Tie2 in endothelial cells, which down-regulated AKT/mTOR signaling. These findings indicate that TBMS1 represents a novel phytochemical for anti-angiogenic treatment of cancer and other angiogenesis-related diseases.
土贝母苷甲（TBMS1）是一种有效的抗肿瘤植物化学物质。然而，其功能和分子作用模式至今仍不清楚。由于血管生成对于肿瘤进展和转移至关重要，我们在此研究了该化合物的抗血管生成作用。在非小细胞肺癌（NSCLC）异种移植模型中，我们发现用TBMS1（5mg/kg）治疗CD1 nu/nu小鼠可显著抑制NCI-H460侧腹肿瘤的生长和血管形成。此外，在大鼠主动脉环试验中，TBMS1呈剂量依赖性地减少血管芽生。在体外，TBMS1诱导内皮细胞凋亡而不降低NSCLC肿瘤细胞的活力，并通过干扰其肌动蛋白丝组织来抑制内皮细胞的迁移。TBMS1还刺激内皮细胞中血管内皮生长因子受体2（VEGFR2）和Tie2的蛋白酶体降解，从而下调AKT/mTOR信号传导。这些发现表明，TBMS1是一种用于癌症和其他血管生成相关疾病抗血管生成治疗的新型植物化学物质。
