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

Journal of Cancer Research and Clinical Oncology
Wei WangGuorong Lv

Abstract

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.

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Citations

Oct 8, 2013·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jia LiuDafang Zhong
Jul 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Claudio ScafoglioErnest M Wright
Jun 21, 2017·Journal of Biomedical Science·Shie-Liang Hsieh, Wan-Wan Lin
Jul 18, 2018·Molecular Medicine Reports·Xiaoliang MaoYeming Wang

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