title: Erythropoietin inhibits apoptosis induced by photodynamic therapy in ovarian cancer cells.
abstract: Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin.
authors.affiliation: Laboratory for Cell and Molecular Biology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.forename: Ján
authors.initials: J
authors.lastname: Koval
authors.forename: Jaromír
authors.initials: J
authors.lastname: Mikes
authors.forename: Ján
authors.initials: J
authors.lastname: Kleban
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Solárová
authors.forename: Ján
authors.initials: J
authors.lastname: Lazúr
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hodorová
authors.forename: Peter
authors.initials: P
authors.lastname: Fedorocko
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Sytkowski
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D011994:Recombinant Proteins
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D004921:Erythropoietin