title: 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.
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 bothin vitroandin vivovia inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0-G1phase, 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 expressionin 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.Mol Cancer Ther; 16(4); 578-90. ©2017 AACR.
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital; Tianjin Gastroenterology and Hepatology Institute, Tianjin 300052, China.
authors.forename: Sinan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jing
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Lingping
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009534:Niclosamide / Q000031:analogs & derivatives; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012458:Salicylanilides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012458:Salicylanilides; D051176:beta Catenin; D009534:Niclosamide