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Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 6, pp 1421–1430 | Cite as

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

  • Shuang-Jia Wang
  • Bei Sun
  • Zhuo-Xin Cheng
  • Hao-Xin Zhou
  • Yue Gao
  • Rui Kong
  • Hua Chen
  • Hong-Chi Jiang
  • Shang-Ha Pan
  • Dong-Bo Xue
  • Xue-Wei Bai
Original Article

Abstract

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.

Keywords

Pancreatic cancer Dihydroartemisinin Antiangiogenesis Nuclear factor-κB 

Notes

Acknowledgments

This work was supported in part by grants from the New Century Support Foundation for Elitist of Chinese Ministry of Education (NCET-07-0248), the Scientific Foundation for Prominent Youth of Heilongjiang Province, China (JC200717), the Scientific and Technological Project of Heilongjiang Province, China (GC09C407-2), and the National Natural Scientific Foundation of China (30571808, 30872987). The authors would like to extend their gratefulness to Ming Mu for her technical assistance.

Conflict of interest

No conflict of interest.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shuang-Jia Wang
    • 1
    • 2
  • Bei Sun
    • 1
  • Zhuo-Xin Cheng
    • 1
  • Hao-Xin Zhou
    • 1
  • Yue Gao
    • 1
    • 3
  • Rui Kong
    • 1
  • Hua Chen
    • 1
  • Hong-Chi Jiang
    • 1
  • Shang-Ha Pan
    • 1
  • Dong-Bo Xue
    • 1
  • Xue-Wei Bai
    • 1
  1. 1.Department of Pancreatic and Biliary SurgeryThe First Affiliated Hospital of Harbin Medical UniversityNangang, HarbinPeople’s Republic of China
  2. 2.Department of Hepato-Biliary-Pancreatic and Vascular SurgeryThe First Affiliated Hospital of Xiamen UniversityXiamenPeople’s Republic of China
  3. 3.Department of Surgery, University HospitalsCase Western Reserve UniversityClevelandUSA

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