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Induction of phosphatase shatterproof 2 by evodiamine suppresses the proliferation and invasion of human cholangiocarcinoma. | LitMetric

Induction of phosphatase shatterproof 2 by evodiamine suppresses the proliferation and invasion of human cholangiocarcinoma.

Int J Biochem Cell Biol

Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 You Zheng Street, Harbin 150001, Heilongjiang, China. Electronic address:

Published: March 2019

AI Article Synopsis

  • Cholangiocarcinoma (CCA) is a deadly cancer with limited treatment options, highlighting the need for new therapies.
  • In this study, evodiamine, a compound from traditional Chinese medicine, demonstrated the ability to inhibit CCA cell growth and promote cell death, while also preventing cell migration and invasion.
  • The research revealed that evodiamine works by suppressing IL-6/STAT3 signaling through enhanced levels of SHP-2, and it was also effective in reducing tumor growth in mouse models.

Article Abstract

Cholangiocarcinoma (CCA) is one of the most common fatal carcinomas and is well known to be lack of effective treatment. Thus, novel therapeutic strategies are greatly needed. Evodiamine, a quinozole alkaloid isolated from evodia rutaecarpa Bentham, has been demonstrated to exhibit anti-tumor effects on many cancer cells. However, little is known in terms of the effects on cholangiocarcinoma. In this study, we studied whether this traditional Chinese Medicine could serve as new potential therapeutic drugs to treat CCA. We discovered that evodiamine inhibited CCA cell proliferation and induced apoptosis. Moreover, evodiamine inhibited CCA cell migration and invasion. Mechanistically, our studies demonstrated that evodiamine inhibited the activation of IL-6 -induced STAT3 signaling activation, and the inhibitory effect was likely due to the upregulation of phosphatase shatterproof 2 (SHP-2), a negative feedback regulator of IL-6/STAT3. Blockage of SHP-2 through small interference RNA (siRNA) abolished the evodiamine -induced IL-6/STAT3 signaling inhibition. Moreover, in vivo experiment showed evodiamine inhibited the tumor growth of nude mice bearing TFK-1 xenografts. In summary, our results implied evodiamine as a promising anti-cancer agent in the treatment of CCA, and the mechanism is likely due to the inhibition of IL-6/STAT3 signaling with upregulating the expression levels of SHP-2.

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Source
http://dx.doi.org/10.1016/j.biocel.2019.01.012DOI Listing

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