Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis

• Published in: PloS one Vol. 7; no. 8; p. e42146
• Main Authors: Lin, Sheng-Zhang, Wei, Wei-Tian, Chen, Hui, Chen, Kang-Jie, Tong, Hong-Fei, Wang, Zhao-Hong, Ni, Zhong-Lin, Liu, Hai-Bin, Guo, Hong-Chun, Liu, Dian-Lei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.08.2012; Public Library of Science (PLoS)
• Subjects: Analysis; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - toxicity; Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Antitumor activity; Apoptosis; Apoptosis - drug effects; Biology; Cancer; Cancer treatment; Cell growth; Cell Line, Tumor; Chemistry; Emodin; Emodin - pharmacology; Emodin - toxicity; Enzyme Activation - drug effects; Female; Gelatinase A; Gelatinase B; Gemcitabine; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - genetics; Medicine; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Nitric Oxide Synthase Type III - genetics; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Phosphorylation; Promotion; Rodents; Surgical implants; Tissues; Tumor Burden - drug effects; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptors; Vascular Endothelial Growth Factors - genetics; Xenograft Model Antitumor Assays; Zhang Lin; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042146

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. 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. 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.