Suppression of the growth and invasion of human head and neck squamous cell carcinomas via regulating STAT3 signaling and the miR-21/β-catenin axis with HJC0152

Yu Wang, Sinan Wang, Yansheng Wu, Yu Ren, Zhaoqing Li, Xiaofeng Yao, Chao Zhang, Na Ye, Chao Jing, Jiabin Dong, Kailiang Zhang, Shanshan Sun, Minghui Zhao, Wenyu Guo, Xin Qu, Yu Qiao, Haiying Chen, Lingping Kong, Rui Jin, Xudong WangLun Zhang, Jia Zhou, Qiang Shen, Xuan Zhou

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0-G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of miR-21. Loss of function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC.

Original languageEnglish (US)
Pages (from-to)578-590
Number of pages13
JournalMolecular Cancer Therapeutics
Volume16
Issue number4
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Wang, Y., Wang, S., Wu, Y., Ren, Y., Li, Z., Yao, X., Zhang, C., Ye, N., Jing, C., Dong, J., Zhang, K., Sun, S., Zhao, M., Guo, W., Qu, X., Qiao, Y., Chen, H., Kong, L., Jin, R., ... Zhou, X. (2017). Suppression of the growth and invasion of human head and neck squamous cell carcinomas via regulating STAT3 signaling and the miR-21/β-catenin axis with HJC0152. Molecular Cancer Therapeutics, 16(4), 578-590. https://doi.org/10.1158/1535-7163.MCT-16-0606