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Journal of Cancer Research and Clinical Oncology

, Volume 138, Issue 9, pp 1597–1605 | Cite as

Triptolide triggers the apoptosis of pancreatic cancer cells via the downregulation of Decoy receptor 3 expression

  • Wei WangEmail author
  • Xinfeng Li
  • Weimin Sun
  • Lurong Zhang
  • Mei Zhang
  • Benzu Hong
  • Guorong Lv
Original Paper

Abstract

Purpose

Triptolide (TPL) is a diterpenoid triepoxide that effectively induces apoptosis in a wide variety of cancer cells. However, the detailed mechanism by which TPL activates caspase cascade remains elusive. This study aimed to examine the antitumor effects of TPL against pancreatic cancer and investigate the underlying mechanism.

Methods

Cell proliferation was evaluated by sulforhodamine B assay. The apoptosis was evaluated by caspase activity assay, Western blot and flow cytometry. DcR3 level was measured by ELISA. AsPC-1 xenografts were established to compare the in vivo antitumor effects of TPL and Gemcitabine.

Results

TPL inhibited the proliferation and induced the apoptosis of pancreatic cancer cells in a dose- and time-dependent manner. TPL also inhibited DcR3 expression in a dose- and time-dependent manner. siRNA-mediated DcR3 knockdown sensitized pancreatic cancer cells to TPL-induced apoptosis. In vivo, DcR3 siRNA significantly enhanced TPL-induced apoptosis and tumor growth inhibition. Moreover, TPL showed less toxicity compared to Gemcitabine in mice model.

Conclusions

TPL induces the apoptosis of pancreatic cancer cells via the downregulation of DcR3 expression and has the potential as an effective agent against pancreatic cancer.

Keywords

Triptolide Apoptosis Decoy receptor 3 Pancreatic cancer 

Notes

Acknowledgments

We thank Dr. Chaoping Ye and Shuangta Xu for helpful suggestion. This work was supported by Natural Science Fund of China (No. 81071968), the Key Program of Scientific Research of FMU (No. 09ZD014, FPNSFC 2008J0079) and Natural Science Fund of Quanzhou (No. 2008Z25).

Conflict of interest

We declare that we have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Wei Wang
    • 1
    Email author
  • Xinfeng Li
    • 1
  • Weimin Sun
    • 2
  • Lurong Zhang
    • 3
  • Mei Zhang
    • 3
  • Benzu Hong
    • 1
  • Guorong Lv
    • 4
  1. 1.Department of General SurgerySecond Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
  2. 2.Department of ImmunologySecond Military Medical CollegeShanghaiChina
  3. 3.Department of Radiation OncologyUF Shands Cancer Center, University of FloridaGainesvilleUSA
  4. 4.Department of UltrasoundSecond Affiliated Hospital of Fujian Medical UniversityQuanzhouChina

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