title: Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microRNA-21 by targeting PTEN, RECK and Bcl-2.
abstract: Icariin is the main active ingredient found in the traditional Chinese medicinal plant Epimedium, and exhibits various pharmacological effects such as enhanced immune function, anticancer activity, improved cardiovascular function and endocrine adjustment. However, the effect of icariin on ovarian cancer and the related mechanism have never been investigated. In the present study, we aimed to verify whether icariin inhibits the proliferation and increases the apoptosis of human ovarian cancer cells, and its molecular mechanism in order to establish an association and identify potential therapeutic targets. In the present study, ovarian cancer A2780 cells were treated with various concentrations of icariin, and the cell viability was evaluated by 3,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry and caspase-3 colorimetric assay were performed to observe apoptotic changes in the A2780 cells. qPCR analysis was used to analyze miR-21 expression in the A2780 cells. Western blot analysis was used to assess PTEN, RECK and Bcl-2 protein expression. Transfection of microRNA-21 (miR-21) and anti-miR-21 was used to investigate expression of its target genes associated with cell proliferation and apoptosis. Icariin concomitantly suppressed cell proliferation, accelerated apoptosis and increased caspase-3 activity in the A2780 cells. In the ovarian cancer A2780 cells, icariin substantially decreased the miR-21 expression level, increased PTEN and RECK protein expression levels and decreased the Bcl-2 protein expression level. Notably, miR-21 regulated the potential anticancer effects of icariin on cell proliferation and apoptosis by targeting PTEN, RECK and Bcl-2 in the ovarian cancer A2780 cells. Our results demonstrated that icariin is an excellent candidate antitumor agent which exhibits an anticancer curative effect on ovarian cancer cells. miR-21 and its target genes may play a vital role in the molecular mechanism of the anticancer effects of icariin.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 100004, P.R. China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 100004, P.R. China.
authors.forename: Kailei
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 100004, P.R. China.
authors.forename: Fujie
authors.initials: F
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D058851:GPI-Linked Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005419:Flavonoids; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C115460:RECK protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C056599:icariin