The activation of STAT3 signaling cascade has been linked with cell survival, proliferation, and angiogenesis in HCC. Literature have shown that overexpression of SHP-1 suppressed cell proliferation in varies cancer cells. Compounds that can activate SHP-1 and further repress STAT3 activity pathway have potential for treatment of HCC. We investigated whether imidazole derivates can modulate the SHP-1/STAT3 pathway. The result showed that imidazole derivate inhibited both constitutive and interleukin 6-inducible STAT3 phosphorylation in HCC cells and induced cell apoptosis. In addition, we explored protein tyrosine phosphatases (SHP-1 and SHP-2) expression level in HCC cells with the treatment of the imidazole derivate. Interestingly, the imidazole derivate significantly induced the expression of SHP1 and subsequently inhibited the phosphorylation of Src , Jak2 and STAT3. This agent also repressed the expression of STAT3-regulated target genes, including cyclin D1, Mcl-1, and survivin. Overall, our results suggest that the imidazole derivate blocks STAT3 activation through up-regulation of SHP-1, and this may have potential for combination with other chemotherapeutic agents.

Citation Format: Jung-Chen Su, Szu-Hsien Wu, Kuen-Feng Chen, Wei-Tien Tai, Jui-Wen Huang, Chung-Wai Shiau. A novel imidazole derivate inhibits STAT3 activation via induction of SHP-1 hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2014-3807

©2014 American Association for Cancer Research.
2014