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

ABSTRACT:

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.

SUBMITTER: Jiang X 

PROVIDER: S-EPMC6296682 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature