Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-κB pathway

• Published in: Cancer chemotherapy and pharmacology 2011-12, Vol.68 (6), p.1421-1430
• Main Authors: Wang, Shuang-Jia, Sun, Bei, Cheng, Zhuo-Xin, Zhou, Hao-Xin, Gao, Yue, Kong, Rui, Chen, Hua, Jiang, Hong-Chi, Pan, Shang-Ha, Xue, Dong-Bo, Bai, Xue-Wei
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic agents; Artemisinins - pharmacology; Biological and medical sciences; Cancer Research; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Endothelial Cells - drug effects; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Neovascularization, Pathologic - prevention & control; NF-kappa B - antagonists & inhibitors; Oncology; Original Article; Pancreatic Neoplasms - blood supply; Pancreatic Neoplasms - drug therapy; Pharmacology. Drug treatments; Pharmacology/Toxicology; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-011-1643-7

Purpose Dihydroartemisinin (DHA) has recently shown antitumor activity in human pancreatic cancer cells. However, its effect on antiangiogenic activity in pancreatic cancer is unknown, and the mechanism is unclear. This study was aimed to investigate whether DHA would inhibit angiogenesis in human pancreatic cancer. Methods Cell viability and proliferation, tube formation of human umbilical vein endothelial cells (HUVECs), nuclear factor (NF)-κB DNA-binding activity, expressions of vascular endothelial growth factor (VEGF), interleukin (IL)-8, cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9 were examined in vitro. The effect of DHA on antiangiogenic activity in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice. Results DHA inhibited cell proliferation and tube formation of HUVECs in a time- and dose-dependent manner and also reduced cell viability in pancreatic cancer cells. DHA significantly inhibited NF-κB DNA-binding activity, so as to tremendously decrease the expression of NF-κB-targeted proangiogenic gene products: VEGF, IL-8, COX-2, and MMP-9 in vitro. In vivo studies, DHA remarkably reduced tumor volume, decreased microvessel density, and down-regulated the expression of NF-κB-related proangiogenic gene products. Conclusions Inhibition of NF-κB activation is one of the mechanisms that DHA inhibits angiogenesis in human pancreatic cancer. We also suggest that DHA could be developed as a novel agent against pancreatic cancer.