title: Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin.
abstract: Recent studies suggest that erythropoietin plays an important role in the process of neoplastic transformation and malignant phenotype progression observed in malignancy. To study the role of erythropoietin and its receptor (EPOR) on the response of cancer cells in vitro, we used two solid tumor cell lines, namely the human malignant glioma cell line U87 and the primary cervical cancer cell line HT100. All experiments were done with heat-inactivated fetal bovine serum in order to inactivate any endogenous bovine erythropoietin. The expression of the EPOR in these cells was confirmed with immunoblot techniques. The addition of exogenous recombinant human erythropoietin (rhEPO) induces the cancer cells to become more resistant to ionizing radiation and to cisplatin. Furthermore, this rhEPO-induced resistance to ionizing radiation and to cisplatin was reversed by the addition of tyrphostin (AG490), an inhibitor of JAK2. Our findings indicate that rhEPO result in a significant, JAK2-dependent, in vitro resistance to ionizing radiation and to cisplatin in the human cancer cells lines studied in this report.
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Alexandre I
authors.initials: AI
authors.lastname: Belenkov
authors.forename: George
authors.initials: G
authors.lastname: Shenouda
authors.forename: Ekatarina
authors.initials: E
authors.lastname: Rizhevskaya
authors.forename: Denis
authors.initials: D
authors.lastname: Cournoyer
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Belzile
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: Slobodan
authors.initials: S
authors.lastname: Devic
authors.forename: Terry Y K
authors.initials: TY
authors.lastname: Chow
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004921:Erythropoietin / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D053614:Janus Kinase 2; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D020032:Tyrphostins / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D002945:Cisplatin