Abstract
Background:
Emodin has been showed to induce apoptosis of pancreatic cancer cells and inhibit tumor growth in our previous studies. This study was designed to investigate whether emodin could inhibit the angiogenesis of pancreatic cancer tissues and its mechanism.
Methodology/principal finding:
In accordance with our previous study, emodin inhibited pancreatic cancer cell growth, induced apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner cells in vitro and in vivo by inhibiting the activity of NF-κB. Here, for the first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and in implanted pancreatic cancer tissues, decreased the expression of angiogenesis-associated factors (NF-κB and its regulated factors VEGF, MMP-2, MMP-9, and eNOS), and reduced eNOS phosphorylation, as evidenced by both immunohistochemistry and western blot analysis of implanted tumors. In addition, we found that emodin had no effect on VEGFR expression in vivo.
Conclusions/significance:
Our results suggested that emodin has potential anti-tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis and suppression of angiogenesis, probably through regulating the expression of NF-κB and NF-κB-regulated angiogenesis-associated factors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / toxicity
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / toxicity
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Apoptosis / drug effects*
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Cell Line, Tumor
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Emodin / pharmacology
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Emodin / toxicity
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Enzyme Activation / drug effects
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 9 / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology*
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Nitric Oxide Synthase Type III / genetics
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism*
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Pancreatic Neoplasms / pathology*
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Tumor Burden / drug effects
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Vascular Endothelial Growth Factors / genetics
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Xenograft Model Antitumor Assays
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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NF-kappa B
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Vascular Endothelial Growth Factors
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Nitric Oxide Synthase Type III
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Emodin
Grants and funding
The authors are grateful for funding support from: The Administration of Traditional Chinese Medicine of Zhengjing Province, China (Grant No. 2011ZZ010), Zhejiang Provincial Science Fund for Distinguished Young Scholars (Grant No. LR12H280001) and The National Natural Science Foundation of China (Grant No. 81173606). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.