Salinomycin inhibits hepatocellular carcinoma cell invasion and migration through JNK/JunD pathway-mediated MMP9 expression

Xu,Ling; Wang,Ting; Meng,Wen-Ying; Wei,Jue; Ma,Jia-Li; Shi,Min; Wang,Yu-Gang

doi:10.3892/or.2014.3680

Salinomycin inhibits hepatocellular carcinoma cell invasion and migration through JNK/JunD pathway-mediated MMP9 expression

Authors:
- Ling Xu
- Ting Wang
- Wen-Ying Meng
- Jue Wei
- Jia-Li Ma
- Min Shi
- Yu-Gang Wang
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Affiliations: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
Published online on: December 18, 2014 https://doi.org/10.3892/or.2014.3680
Pages: 1057-1063
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The antibiotic salinomycin (Salin) was recently identified as an antitumor drug for the treatment of several types of solid tumors. However, the effects of Salin on the migratory and invasive properties of hepatocellular carcinoma (HCC) cells are unclear. The present study aimed to determine the antitumor efficacy and mechanism of Salin in HCC cells. Human HCC cells (HCCLM3) treated with Salin showed a concentration-dependent reduction in cell migration and invasion, and this was associated with reduced MMP9 expression. The MMP9 promoter and enhancer in a luciferase reporter assay revealed that Salin can regulate MMP9 expression through an activator protein (AP-1) site within the MMP9 enhancer. JunD, one of the AP-1 components, was significantly decreased by Salin in a concentration- and time-dependent manner. Salin was able to induce c-Jun NH2-kinase (JNK) phosphorylation and to block both JunD and MMP9 expression. Our results showed that JNK phosphorylation and JunD may be involved in the Salin-regulated MMP9 signaling pathway in HCCLM3 cells and may mediate HCC cell biological characteristics. Our studies provide new insight into the antitumor effects of Salin.

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