Published in:
Open Access 01-12-2013 | Primary research
Inhibition of the angiogenesis and growth of Aloin in human colorectal cancer in vitro and in vivo
Published in: Cancer Cell International | Issue 1/2013
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Background
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.
Method
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.
Results
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.
Conclusion
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.