A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down-Regulation of Vascular Endothelial Growth Factor Receptor-2 and Suppresses Tumor Growth In Vivo
A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down-Regulation of Vascular Endothelial Growth Factor Receptor-2 and Suppresses Tumor Growth In Vivo
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DOI：
10.1002/anie.201608094
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发表时间：
2016-10-17
影响因子：
16.6
通讯作者：
Che, Chi-Ming
中科院分区：
文献类型：
--
作者：
Kwong, Wai-Lun;Lam, Kar-Yee;Che, Chi-Ming
大环钌（III）配合物[Ru-III(N2O2)Cl-2]Cl （Ru-1）被报道为血管生成抑制剂和抗肿瘤化合物。该复合物在体外对内皮细胞和癌细胞系相对无细胞毒性，但能特异性抑制血管生成内皮细胞管形成和癌细胞侵袭过程。此外，与已知的抗癌钌复合物相比，Ru-1的独特之处在于它抑制血管内皮生长因子受体-2 （VEGFR2）的表达，以及对肿瘤血管生成至关重要的相关下游信号的表达。此外，体内研究表明，Ru-1在斑马鱼模型中抑制血管生成，并抑制肿瘤移植裸鼠的肿瘤生长。
A macrocyclic ruthenium(III) complex [Ru-III(N2O2)Cl-2]Cl (Ru-1) is reported as an inhibitor of angiogenesis and an anti-tumor compound. The complex is relatively non-cytotoxic towards endothelial and cancer cell lines invitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti-cancer ruthenium complexes, Ru-1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor-2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, invivo studies showed that Ru-1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts.