Low concentration of formononetin promotes proliferation of estrogen receptor-positive cells through an ER?-miR-375-PTEN-ERK1/2-bcl-2 pathway.

ABSTRACT: A low dose of formononetin accelerates the proliferation of nasopharyngeal carcinoma cells in vitro; however, the underlying mechanism remains unknown. Here, we investigated the molecular mechanism of formononetin in CNE2 cell proliferation. CNE2 cells were treated with 0 to 1 ?M formononetin. To inhibit mitogen activated protein kinase / extracellular regulate kinase (MAPK/ERK) kinase (MEK) and microRNA (miR)-375, cells were pretreated with either PD98059 or a miR-375 inhibitor, respectively, followed by co-treatment with formononetin (0.3 ?M) plus an inhibitor. Female rats were ovariectomized (OVX), and some OVX rats received formononetin or estrogen (E₂) injections. Sham operated animals were used as controls. Compared to control, 0.3 ?M formononetin accelerated proliferation and decreased late apoptosis of CNE2 cells. However, formononetin-induced pro-growth and anti-apoptosis activity was abolished by PD98059 and the miR-375 inhibitor. In addition, 0.1 and 0.3 ?M formononetin significantly increased estrogen receptor-? (ER?) and bcl-2, but decreased protein-phosphatase and tensin homologue (PTEN) protein expression, all of which was reversed by the miR-375 inhibitor. Additionally, formononetin treatment resulted in a transient upregulation of phosphorylated (p)-ERK1/2. In vivo studies indicated that formononetin significantly increased endometrium thickness and down-regulated ER? expression in OVX rats. Taken together, our study demonstrates that a low concentration of formononetin can promote growth of CNE2 cells and uterine tissues, possibly through regulating the ER?-miR-375-PTEN-ERK1/2-bcl-2 signaling pathway.

SUBMITTER: Guo YH 

PROVIDER: S-EPMC5725001 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature