Journal
MOLECULAR CANCER THERAPEUTICS
Volume 16, Issue 4, Pages 578-590Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-16-0606
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Funding
- China National Natural Scientific Fund [81572492]
- National Institutes of Health R01 grant [DA038446]
- Cancer Prevention Research Institute of Texas award
- John Sealy Memorial Endowment Fund
- Institute for Translational Sciences at UTMB
- Cancer Center Support Grant from the NIH/NCI [CA016672]
- MDACC
- Duncan Family Institute Seed Funding Research Program
- Holden Family Research Grant in Breast Cancer Prevention, Prevent Cancer Foundation
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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/beta-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/beta-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/beta-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. (C)2017 AACR.
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