title: Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway.
abstract: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β,β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Peishu
authors.identifier: 0000-0002-1257-7144
authors.initials: P
authors.lastname: Liu
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D062445:Claudin-1 / Q000096:biosynthesis; D004642:Emodin / Q000008:administration & dosage*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008301:Maleimides / Q000008:administration & dosage; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis; D000099200:Scaffold Protein ILK
chemical_list: D015820:Cadherins; D062445:Claudin-1; D004642:Emodin; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles; D008301:Maleimides; D017346:Protein Serine-Threonine Kinases; D000071250:Snail Family Transcription Factors; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C568108:CLDN1 protein, human; C417521:SB 216763; C000604407:SNAI1 protein, human