Norcantharidin inhibits IL-6-induced epithelial‑mesenchymal transition via the JAK2/STAT3/TWIST signaling pathway in hepatocellular carcinoma cells.

Abstract

Epithelial-mesenchymal transition (EMT), plays a vital role in hepatocellular carcinoma (HCC) development and metastasis. Norcantharidin (NCTD; 7-oxabicyclo (2.2.1) heptane-2,3-dicarboxylic anhydride) plays anticancer roles in the regulation of tumor cell proliferation, apoptosis and migration. However, the molecular mechanism of HCC EMT and the effects of NCTD in the HCC EMT process have been either poorly elucidated or not studied. In this study, HCC EMT was induced by the treatment of IL-6 and various concentrations of NCTD (0, 30, 60 and 120 µM) were treated with HCC cell lines, HCCLM3 and SMMC-7721. We investigated the effect of NCTD on the invasion of HCC cells by using Transwell assay. Immunofluorescence staining, western blot analysis and quantitative RT-PCR were performed to evaluate the protein and mRNA expression levels of HCC cells. Here, using cell line models, our data demonstrated that interleukin 6 (IL-6) induced EMT through the JAK/STAT3/TWIST pathway in HCC. Moreover, our studies revealed that NCTD markedly inhibited IL-6-induced EMT and cell invasiveness. Signaling studies revealed that NCTD sufficiently suppressed JAK/STAT3/TWIST signaling to reverse the IL-6-promoting effects. Collectively, these data provide evidence for the use of NCTD as a potential anticancer drug in HCC metastatic patients.

• Authors: Yebo Gao, Weidong Li, Rui Liu, Qiujun Guo, Jie Li, Yanju Bao, Honggang Zheng, Shulong Jiang, Baojin Hua
• Journal: Oncology reports (Oncol Rep) Vol. 38 Issue 2 Pg. 1224-1232 (Aug 2017) ISSN: 1791-2431 [Electronic] Greece
• PMID: 28677802 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Bridged Bicyclo Compounds, Heterocyclic
• IL6 protein, human
• Interleukin-6
• STAT3 Transcription Factor
• Twist-Related Protein 1
• norcantharidin
• JAK2 protein, human
• Janus Kinase 2

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Biomarkers, Tumor
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Interleukin-6 (pharmacology)
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Neoplasm Invasiveness
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Tumor Cells, Cultured
• Twist-Related Protein 1 (antagonists & inhibitors, metabolism)