JNK inhibitor SP600125 enhances TGF‑β‑induced apoptosis of RBE human cholangiocarcinoma cells in a Smad‑dependent manner

  • Authors:
    • Youzhi Lin
    • Binhao Zhang
    • Huifang Liang
    • Yulei Lu
    • Xi Ai
    • Bixiang Zhang
    • Xiaoping Chen
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  • Published online on: October 2, 2013     https://doi.org/10.3892/mmr.2013.1711
  • Pages: 1623-1629
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Abstract

Transforming growth factor β (TGF‑β) signaling is pivotal for the progression of specific types of tumors at certain stages. However, the mechanism by which TGF‑β is regulated by other factors remains unclear. In this study, the involvement of SP600125, an inhibitor of c‑Jun N‑terminal kinase (JNK), in TGF‑β‑induced apoptosis of the RBE human cholangiocarcinoma cell line was investigated. Exogenous TGF‑β1 activated Smad and non‑Smad signaling pathways, including the JNK pathway in RBE cells, and induced apoptosis, which was inhibited by knockdown of Smad4 expression. SP600125 increased the TGF‑β1‑induced phosphorylation of Smad2 and Smad3, which enhanced the TGF‑β1‑induced transcriptional response and apoptosis in RBE cells. The effect of SP600125 on the transcriptional response and apoptosis was reduced by knockdown of Smad4 expression. In addition, TGF‑β1‑induced apoptosis was abrogated using the pan‑caspase inhibitor Z‑VAD‑fmk. SP600125 promoted the TGF‑β1‑induced caspase cleavage, while knockdown of Smad4 expression counteracted this effect. These results indicate that SP600125 enhances TGF‑β‑induced apoptosis of RBE cells through a Smad‑dependent pathway that involves Smad‑dependent caspase activation. SP600125 is hypothesized to be an ideal therapeutic candidate for treating human cholangiocarcinoma.
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December 2013
Volume 8 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lin Y, Zhang B, Liang H, Lu Y, Ai X, Zhang B and Chen X: JNK inhibitor SP600125 enhances TGF‑β‑induced apoptosis of RBE human cholangiocarcinoma cells in a Smad‑dependent manner. Mol Med Rep 8: 1623-1629, 2013.
APA
Lin, Y., Zhang, B., Liang, H., Lu, Y., Ai, X., Zhang, B., & Chen, X. (2013). JNK inhibitor SP600125 enhances TGF‑β‑induced apoptosis of RBE human cholangiocarcinoma cells in a Smad‑dependent manner. Molecular Medicine Reports, 8, 1623-1629. https://doi.org/10.3892/mmr.2013.1711
MLA
Lin, Y., Zhang, B., Liang, H., Lu, Y., Ai, X., Zhang, B., Chen, X."JNK inhibitor SP600125 enhances TGF‑β‑induced apoptosis of RBE human cholangiocarcinoma cells in a Smad‑dependent manner". Molecular Medicine Reports 8.6 (2013): 1623-1629.
Chicago
Lin, Y., Zhang, B., Liang, H., Lu, Y., Ai, X., Zhang, B., Chen, X."JNK inhibitor SP600125 enhances TGF‑β‑induced apoptosis of RBE human cholangiocarcinoma cells in a Smad‑dependent manner". Molecular Medicine Reports 8, no. 6 (2013): 1623-1629. https://doi.org/10.3892/mmr.2013.1711