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.

MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression

“…MiR-21 is highly expressed in multiple cancers, such as epithelial cell cancer, connective tissue cancer, hematopoietic cell cancer, reproductive cell cancer and nerve cell cancer [9]. Previous studies have demonstrated that the target genes of miR-21 including phosphatase and tensin homolog detected on chromosome 10 (PTEN), Bcl-2 , TPM1 and PDCD4 which are cancer suppressed genes [10–13]. Previous studies have shown that miR-21 regulates PTEN by interacting with its target gene 3′-UTR and participates in the process of cancer occurrence and development [14–15].…”

Nimbolide upregulates RECK by targeting miR-21 and HIF-1α in cell lines and in a hamster oral carcinogenesis model

“…Recently, Li et al . 39 demonstrated that iicarin, an active ingredient of the Chinese medicinal plant Epimedium regulates proliferation and apoptosis of human ovarian cancer cells by targeting miR-21 and substantially increasing RECK protein expression. Curcumin was shown to inhibit the growth of oesophageal cancer cell lines by inhibiting Notch signaling and Notch-specific miR-21 40 .…”

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

“…Thus there is a feedback loop between RECK, STAT3 and MMPs, suggesting the up-expression of the tumor suppressor RECK may influence the signal transduction of STAT3 and MMPs. Notably, several previous studies reported that up-regulation of RECK resulted in decreased ovarian cancer amplification [14]. In addition, histone deacetylase inhibitor inhibited ovarian cancer cell migration partially through up-regulation of RECK [15].…”