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 language | English (US) |
|---|---|
| Pages (from-to) | 578-590 |
| Number of pages | 13 |
| Journal | Molecular Cancer Therapeutics |
| Volume | 16 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2017 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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. / Wang, Yu; Wang, Sinan; Wu, Yansheng; Ren, Yu; Li, Zhaoqing; Yao, Xiaofeng; Zhang, Chao; Ye, Na; Jing, Chao; Dong, Jiabin; Zhang, Kailiang; Sun, Shanshan; Zhao, Minghui; Guo, Wenyu; Qu, Xin; Qiao, Yu; Chen, Haiying; Kong, Lingping; Jin, Rui; Wang, Xudong; Zhang, Lun; Zhou, Jia; Shen, Qiang; Zhou, Xuan.
In: Molecular Cancer Therapeutics, Vol. 16, No. 4, 01.04.2017, p. 578-590.Research output: Contribution to journal › Article
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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
PY - 2017/4/1
Y1 - 2017/4/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=85017031202&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-16-0606
DO - 10.1158/1535-7163.MCT-16-0606
M3 - Article
VL - 16
SP - 578
EP - 590
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 4
ER -