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.
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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).
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We declare that we have no conflict of interest.
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Wang, W., Li, X., Sun, W. et al. Triptolide triggers the apoptosis of pancreatic cancer cells via the downregulation of Decoy receptor 3 expression. J Cancer Res Clin Oncol 138, 1597–1605 (2012). https://doi.org/10.1007/s00432-012-1235-x
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DOI: https://doi.org/10.1007/s00432-012-1235-x