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Am J Cancer Res. 2019 Apr 1;9(4):699-713. eCollection 2019.

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

Author information

1
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.
2
Research Center of Basic Medical Sciences, Tianjin Medical University Tianjin 300070, China.
3
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center Houston, Texas 77030, USA.
4
Department of Pharmacology and Toxicology Member, University of Texas Medical Branch Galveston, Texas 77555, USA.

Abstract

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.

KEYWORDS:

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

PMID:
31105997
PMCID:
PMC6511646

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