Emodin inhibits epithelial to mesenchymal transition in epithelial ovarian cancer cells by regulation of GSK-3β/β-catenin/ZEB1 signaling pathway.

Abstract

Emodin (EMO) has been shown to possess pleiotropic anticancer capabilities in many types of cancer, including epithelial ovarian cancer (EOC). Inhibitory efficacy of EMO on EOC invasion and migration was previously observed, however, the underlying mechanisms have not been completely elucidated. The present study is aimed to explore the mechanisms. Transwell assay demonstrated that EMO significantly inhibited A2780 and SK-OV-3 cell invasion. Western blot analysis was performed to detect the expression levels of epithelial to mesenchymal transition (EMT)-related markers. We found that EMO treatment dose-dependently upregulated E-cadherin, keratin and downregulated N-cadherin, vimentin, matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) to repress EMT. Mechanistically, EMO could inhibit glycogen synthase kinase 3β (GSK-3β) phosphorylation, decrease total β-catenin protein levels and subsequently downregulate transcription factor zinc finger E-box binding homeobox 1 (ZEB1) expression. These effects of EMO were weakened when the cells were pretreated with SB216763, an inhibitor of GSK-3β kinase. Besides, we utilized small interfering RNA (siRNA) to downregulate ZEB1 expression. We found that treatment of ZEB1-knockdown cells with EMO, ZEB1 levels were lowest and cell invasion was weakest but ZEB1 knockdown had no effect on the expression of phospho-Ser9-GSK-3β (p-GSK-3βSer9), β-catenin. In conclusion, our results suggested that EMO inhibited EOC cell invasion by regulation of GSK-3β/β-catenin/ZEB1 signaling pathway to suppress EMT in vitro.

• Authors: Chen Hu, Taotao Dong, Rui Li, Jingjing Lu, Xuan Wei, Peishu Liu
• Journal: Oncology reports (Oncol Rep) Vol. 35 Issue 4 Pg. 2027-34 (Apr 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26820690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• beta Catenin
• Glycogen Synthase Kinase 3 beta
• Emodin

Topics

• Antineoplastic Agents (pharmacology)
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Emodin (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• Neoplasm Invasiveness
• Neoplasms, Glandular and Epithelial (drug therapy, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)
• beta Catenin (metabolism)