A novel STAT3 inhibitor, HJC0152, exerts potent antitumor activity in glioblastoma

American Journal of Cancer Research

Yini Xu¹  Zhaoqing Li²  Chuanqiang Wu³  Tingting Zhu⁴ 

[1] Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA;Department of Maxillofacial and Otorhinolaryngology 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;Department of Pharmacology and Toxicology Member, University of Texas Medical Branch, Galveston, Texas 77555, USA;Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

关键词: HJC0152;    STAT3;    anti-tumor activity;    glioblastoma;    epithelial-mesenchymal transition;    senescence;    apoptosis;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

Aberrant expression and activation of signal transducer and activator of transcription 3 (STAT3) is implicated in several malignancies, including glioblastoma, and is correlated with poor outcomes in patients with glioblastoma, rendering STAT3 a potential therapeutic target. However, few STAT3 inhibitors have been approved for clinical use. We recently developed an orally active small-molecule compound with anti-STAT3 activity, HJC0152. This study aimed to test the effect of this novel drug on glioblastoma cell lines, and provide possibility to improve clinic prognosis of patients with glioblastoma in the future. In the present study, we aimed to determine the effects of HJC0152 on the growth, proliferation, and chemosensitivity of glioblastoma cell lines and xenograft tumors. We found that HJC0152 inactivated STAT3 via inhibiting phosphorylation of the Tyr705 residue. In vitro, HJC0152 suppressed the proliferation and motility of glioblastoma cells, induced apoptosis, and enhanced the chemosensitivity of glioblastoma cells. Furthermore, HJC0152 inhibited the growth of glioblastoma xenograft tumors in vivo. This study provides a rationale for developing HJC0152 as a STAT3-targeting therapy for treating human glioblastoma in the future.

【 授权许可】

CC BY-NC