TY - JOUR
T1 - 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
AU - Wang, Yu
AU - Wang, Sinan
AU - Wu, Yansheng
AU - Ren, Yu
AU - Li, Zhaoqing
AU - Yao, Xiaofeng
AU - Zhang, Chao
AU - Ye, Na
AU - Jing, Chao
AU - Dong, Jiabin
AU - Zhang, Kailiang
AU - Sun, Shanshan
AU - Zhao, Minghui
AU - Guo, Wenyu
AU - Qu, Xin
AU - Qiao, Yu
AU - Chen, Haiying
AU - Kong, Lingping
AU - Jin, Rui
AU - Wang, Xudong
AU - Zhang, Lun
AU - Zhou, Jia
AU - Shen, Qiang
AU - Zhou, Xuan
N1 - Funding Information:
The authors thank Jie Zhao at Tianjin Hospital for his kind assistance. We also thank Amy Ninetto, PhD, ELS, Department of Scientific Publications, The University of Texas MD Anderson Cancer Center, for her editing of the manuscript. This work was supported by the China National Natural Scientific Fund No. 81572492 (X. Zhou), the National Institutes of Health R01 grant DA038446 (J. Zhou), Cancer Prevention Research Institute of Texas award (J. Zhou), the John Sealy Memorial Endowment Fund (J. Zhou), the Institute for Translational Sciences atUTMB(J. Zhou), in part by a Cancer Center Support GrantCA016672 from the NIH/NCI (Q. Shen), Startup fund from MDACC (Q. Shen), Duncan Family Institute Seed Funding Research Program (Q. Shen), and the Holden Family Research Grant in Breast Cancer Prevention, Prevent Cancer Foundation (Q. Shen).
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-16-0606
DO - 10.1158/1535-7163.MCT-16-0606
M3 - Article
C2 - 28138036
AN - SCOPUS:85017031202
VL - 16
SP - 578
EP - 590
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 4
ER -