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Casein kinase 1α-dependent inhibition of Wnt/β-catenin selectively targets nasopharyngeal carcinoma and increases chemosensitivity

Li, Jiangping*,; Jiang, Yan*,; Wang, Pengju; Ke, Saixiong; Yang, Ling; Shen, Ying

doi: 10.1097/CAD.0000000000000747
Preclinical Reports
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Pyrvinium tosylate (PT) is an anthelminthic drug that has recently been shown to suppress various human cancers. However, whether PT is effective in nasopharyngeal carcinoma (NPC) has not been determined to date. In this work, we show the selective efficacy of PT in NPC while sparing normal nasopharyngeal epithelial cells, and its ability to increase chemosensitivity. We show that PT at 100 and 500 nmol/l significantly inhibits growth and induces apoptosis in several NPC cell lines without affecting normal nasopharyngeal epithelial cells. Using cell culture and xenograft mouse models, PT markedly enhances cisplatin’s efficacy in NPC and the combination leads to almost complete tumor inhibition. Mechanism studies show that PT suppresses active, nuclear β-catenin level and activity and increases Axin level in NPC cells. β-Catenin overexpression completely reverses the inhibitory effects of PT, confirming that β-catenin is the molecular mechanism of PT’s action in NPC. In addition, the effects of PT on β-catenin and Axin levels and on Wnt signaling in NPC cells are mediated by its activation of casine kinase 1α. Our work is the first to suggest that Wnt/β-catenin is a selective target for NPC treatment, and provides the preclinical evidence on the translational potential of PT as a useful addition to the treatment armamentarium for NPC.

Department of Otolaryngology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China

* Jiangping Li and Yan Jiang contributed equally to the writing of this article.

Received 22 July 2019 Revised form accepted 27 December 2019

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Correspondenceto Ling Yang, Msc Department of Otolaryngology, Xiangyang Central Hospital, Affiliated Hospital of Hubei university of Arts and Science, 136 Jingzhou Street, Xiangyang 441021, Hubei Province, China Tel: + 86 158 7196 3661; fax: + 86 710 351 2850 e-mail: 52208062@qq.com

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