The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
Cancer Cell Int. 2013 Jul 12;13(1):69. doi: 10.1186/1475-2867-13-69.
Angiogenesis has been an attractive target for drug therapy. Aloin (AL), an natural compound derived from Aloe barbadensis Miller leaves, has been shown to possess anti-cancer potential activities. However, its roles in tumor angiogenesis and the involved molecular mechanism are unknown.
To evaluate the antiangiogenic and anticancer activities of AL, endothelial cell scratch, modified Boyden chamber inserts and tube formation assays were done in HUVECs, and MTT and Live-Dead assays were used to determine the proliferation inhibition and apoptosis induction of colorectal cancer cells in vitro. The inhibition effects of AL were further confirmed by a mouse xenograft model in vivo. The expression levels of STAT3 signaling pathway and that mediated-target genes were measured in HUVECs and SW620 cells by Western blots.
Here, we demonstrated that AL significantly inhibited HUVECs proliferation, migration and tube formation in vitro. Western blotting showed that AL suppressed activation of VEGF receptor (VEGFR) 2 and STAT3 phosphorylation in endothelial cells. In addition, the constitutively activated STAT3 protein, and the expression of STAT3-regulated antiapoptotic (Bcl-xL), proliferative (c-Myc), and angiogenic (VEGF) proteins were also down-regulated in response to AL in human SW620 cancer cells. Consistent with the above findings, AL inhibited tumor cell viability and induced cell apoptosis in vitro, and substantially reduced tumor volumes and weight in vivo mouse xenografts, without obviously toxicity.
Our studies provided the first evidence that AL may inhibit tumor angiogenesis and growth via blocking STAT3 activation, with the potential of a drug candidate for cancer therapy.
血管生成一直是药物治疗的一个有吸引力的靶点。芦荟大黄素 (AL) 是从库拉索芦荟叶中提取的天然化合物，已被证明具有抗癌潜力。然而，它在肿瘤血管生成中的作用及其涉及的分子机制尚不清楚。
为了评估 AL 的抗血管生成和抗癌活性，在 HUVECs 中进行了内皮细胞划痕、改良 Boyden 室插入和管形成测定，并用 MTT 和 Live-Dead 测定法测定了体外结直肠癌细胞的增殖抑制和凋亡诱导作用。在体内小鼠异种移植模型中进一步证实了 AL 的抑制作用。通过 Western blot 测量 HUVECs 和 SW620 细胞中 STAT3 信号通路和介导靶基因的表达水平。
在这里，我们证明 AL 显著抑制了 HUVECs 的增殖、迁移和管形成。Western blot 显示 AL 抑制了内皮细胞中 VEGFR2 和 STAT3 磷酸化的激活。此外，在人 SW620 癌细胞中，AL 还抑制了组成性激活的 STAT3 蛋白和 STAT3 调节的抗凋亡 (Bcl-xL)、增殖 (c-Myc) 和血管生成 (VEGF) 蛋白的表达。与上述发现一致，AL 在体外抑制肿瘤细胞活力并诱导细胞凋亡，并在体内小鼠异种移植中显著降低肿瘤体积和重量，而无明显毒性。
我们的研究首次提供了证据，表明 AL 可能通过阻断 STAT3 激活来抑制肿瘤血管生成和生长，具有作为癌症治疗候选药物的潜力。
