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



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.


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.


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.


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.


Triptolide Apoptosis Decoy receptor 3 Pancreatic cancer 



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.


  1. Bai C, Connolly B, Metzker ML, Hilliard CA, Liu X, Sandig V, Soderman A, Galloway SM, Liu Q, Austin CP, Caskey CT (2000) Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc Natl Acad Sci USA 97:1230–1235PubMedCrossRefGoogle Scholar
  2. Bai J, Sui J, Demirjian A, Vollmer CM Jr, Marasco W, Callery MP (2005) Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro. Cancer Res 65:2344–2352PubMedCrossRefGoogle Scholar
  3. Carter BZ, Mak DH, Schober WD, McQueen T, Harris D, Estrov Z, Evans RL, Andreeff M (2006) Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood 108:630–637PubMedCrossRefGoogle Scholar
  4. Chen J, Zhang L, Kim S (2004) Quantification and detection of DcR3, a decoy receptor in TNFR family. J Immunol Methods 285:63–70PubMedCrossRefGoogle Scholar
  5. Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966PubMedCrossRefGoogle Scholar
  6. Di Marco M, Di Cicilia R, Macchini M, Nobili E, Vecchiarelli S, Brandi G, Biasco G (2010) Metastatic pancreatic cancer: is gemcitabine still the best standard treatment? Oncol Rep 23:1183–1192PubMedGoogle Scholar
  7. Frese S, Pirnia F, Miescher D, Krajewski S, Borner MM, Reed JC, Schmid RA (2003) PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2. Oncogene 22:5427–5435PubMedCrossRefGoogle Scholar
  8. Liang QL, Wang BR, Li GH (2009) DcR3 and survivin are highly expressed in colorectal carcinoma and closely correlated to its clinicopathologic parameters. J Zhejiang Univ Sci B 10:675–682PubMedCrossRefGoogle Scholar
  9. Mujumdar N, Mackenzie TN, Dudeja V, Chugh R, Antonoff MB, Borja-Cacho D, Sangwan V, Dawra R, Vickers SM, Saluja AK (2010) Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology 139:598–608PubMedCrossRefGoogle Scholar
  10. Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A (1998) Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396:699–703PubMedCrossRefGoogle Scholar
  11. Tao X, Younger J, Fan FZ, Wang B, Lipsky PE (2002) Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Arthritis Rheum 46:1735–1743PubMedCrossRefGoogle Scholar
  12. Tsuji S, Hosotani R, Yonehara S, Masui T, Tulachan SS, Nakajima S, Kobayashi H, Koizumi M, Toyoda E, Ito D, Kami K, Mori T, Fujimoto K, Doi R, Imamura M (2003) Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma. Int J Cancer 106:17–25PubMedCrossRefGoogle Scholar
  13. Wang W, Yang S, Su Y, Xiao Z, Wang C, Li X, Lin L, Fenton BM, Paoni SF, Ding I, Keng P, Okunieff P, Zhang L (2007) Enhanced antitumor effect of combined triptolide and ionizing radiation. Clin Cancer Res 13:4891–4899PubMedCrossRefGoogle Scholar
  14. Wu Y, Han B, Sheng H, Lin M, Moore PA, Zhang J, Wu J (2003) Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients. Int J Cancer 105:724–732PubMedCrossRefGoogle Scholar
  15. Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB, Zhang L (2003) Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2:65–72PubMedGoogle Scholar
  16. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (1999) A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. J Biol Chem 274:13733–13736PubMedCrossRefGoogle Scholar
  17. Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho YH, Li Y, Moore PA, Wu J (2001) Modulation of T-cell responses to alloantigens by TR6/DcR3. J Clin Invest 107:1459–1468PubMedCrossRefGoogle Scholar

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

Personalised recommendations