Erythropoietin Potentiates the Anti-Proliferative Effect of Tamoxifen in Ovarian Adenocarcinoma A2780 Cells

Patrícia Kimáková,Barbora Fecková,Nataša Debeljak,Peter Solár,Erika Szentpéteriová

doi:10.17344/acsi.2018.4452

Patrícia Kimáková, Barbora Fecková + Show 3 more

Open Access

https://doi.org/10.17344/acsi.2018.4452

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Abstract

We have recently shown that erythropoietin receptor (EPOR) protects cancer cells from tamoxifen (TAM)-induced cell death in the absence of erythropoietin (EPO). In this study, we analyzed the effect of EPOR silencing and EPO treatment on the response to TAM in human ovarian adenocarcinoma cells A2780. We demonstrated that the EPOR siRNA silencing decreases cell proliferation and sensitizes and/or potentiates the anti-proliferative effect of TAM on A2780 cells. Similarly, the combined effect of EPO and TAM treatment significantly reduced cell proliferation compared to TAM alone. Our in vitro results indicated the need for further investigation of EPO effects on a similar in vivo model.

Highlights

Erythropoietin (EPO) is a glycoprotein, the biological effects of which are mediated through the binding to the EPO receptor (EPOR)
The formation of EPO-EPOR complex resulted in the activation of many proteins,[6] such as Janus kinase (JAK), Signal transducer and activator of transcription (STAT),[7] as well as other signal pathways involved in cell proliferation, survival and/or gene expression control.[8]
Both downregulation of EPOR as well as TAM therapy reduced cell proliferation of A2780 cells compared to controls

Summary

Introduction

Erythropoietin (EPO) is a glycoprotein, the biological effects of which are mediated through the binding to the EPO receptor (EPOR). Silencing of EPOR expression resulted in reduced A2780 proliferation as well as a reduction of EPO-induced ERK1/2 phosphorylation.[5] the formation of EPO-EPOR complex resulted in the activation of many proteins,[6] such as Janus kinase (JAK), Signal transducer and activator of transcription (STAT),[7] as well as other signal pathways involved in cell proliferation, survival and/or gene expression control.[8] The presence of EPOR in tumor cells question its possible negative effects on both tumor cell proliferation and the inhibition of apoptosis. We aimed to analyze the effect of EPOR silencing as well as the effect of EPO treatment on the anti-proliferative potential of TAM therapy in human ovarian adenocarcinoma cells A2780

Experimental

Results and Discussion

Conclusions