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HJC0152, a novel STAT3 inhibitor with promising anti-tumor effect in gastric cancer

Authors Jiang X, Wu M, Xu Z, Wang H, Wang H, Yu X, Li Z, Teng L

Received 21 September 2018

Accepted for publication 15 November 2018

Published 12 December 2018 Volume 2018:10 Pages 6857—6867

DOI https://doi.org/10.2147/CMAR.S188364

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Chien-Feng Li


Xiaoxia Jiang,1,2 Mengjie Wu,1,2 Zhenzhen Xu,1,2 Haohao Wang,1,2 Haiyong Wang,1,2 Xiongfei Yu,1 Zhongqi Li,1 Lisong Teng1,2

1Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, People’s Republic of China

Background: Aberrant activation of the signal transducer and activator of transcription 3 (STAT3) is frequently seen in patients with gastric cancer (GC), and is generally associated with worse prognosis. HJC0152, a novel STAT3 inhibitor, has shown significant anti-tumor effects in several cancers, although its role in GC remains to be clarified.
Methods: The effect of HJC0152 on STAT3 signaling pathway and the biological behaviors of GC cells were evaluated through in vitro and/or in vivo experiments. Meanwhile, RNA sequence analysis was used to further explore its potential anti-tumor mechanisms.
Results: HJC0152 inhibited the expression of activated STAT3 and its downstream target genes (c-Myc and clyclinD1) in GC cells, and restrained tumor growth in vivo. HJC0152 treatment induced apoptosis in the STAT3 hyper-activated AGS and MKN45 cell lines, along with down-regulation of survivin and Mcl1, and up-regulation of cleaved-poly(ADP-ribose) polymerase. Moreover, HJC0152 markedly inhibited migration and invasion of these cells. Finally, RNA sequence analysis and protein expression analyses showed that in addition to STAT3 suppression, HJC0152 also exerts its anti-tumor effects at least partly via the mitogen-activated protein kinases pathway.
Conclusion: Our findings highlight that HJC0152 is a promising therapeutic agent for GC.

Keywords: gastric cancer, inhibitor, HJC0152, STAT3, MAPK

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