title: [Effects and mechanisms of recombinant human erythropoietin in treating multiple myeloma in murine mice].
abstract: OBJECTIVE
  To test the effects and to identify appropriate dosage and possible mechanisms of recombinant human erythropoietin (rHuEPO) in treating MPC-11 myeloma in the BALB/c murine models.
  
  
  METHODS
  A total of 420 BALB/c mice were divided into five groups. 410 of which were injected with 10(4) MPC-11 cells. The 10 mice without myeloma cell inoculation served as normal controls. On the fifth day after inoculation, 50 tumor-bearing mice were arbitrarily assigned into the placebo group, while the other 360 mice were randomly allocated into three experimental groups. Each experimental group had 120 mice and received 10, 20 and 30 units subcutaneous injection of rHuEPO, respectively. A daily injection was administered for 14 days, followed by three injections per week. The mice in the placebo group were administered with saline following the same scheme. Dynamic monitoring of serum M-protein and hemoglobin levels of the mice were performed after myeloma cell inoculation. The subcutaneous nodules were sent for pathological biopsy to ascertain the successful establishment of the murine models. The mice were randomly chosen from each group to be tested for the levels of monoclonal IgG and kappa light chain in their sera (immunofixation electrophoresis and ELISA), counts of CD4 and CD8 positive cells in whole blood (flow cytometry), microvessel density (by marking CD31) and cell apoptosis (TdT-mediated dUTP-biotin nick end labeling, TUNEL) of tumor tissues, as well as the levels of cytokines such as IL-6 and TNF-alpha in sera (ELISA) at each month after the injection of rHuEPO.
  
  
  RESULTS
  The serum monoclonal immunoglobulin appeared on the 22nd day after inoculation of MPC-11 cells. rHuEPO increased Hb level and survival time of the mice with multiple myeloma. The serum levels of IL-6, IgG and kappa light chain decreased significantly in the mice in the treatment groups compared with those in the placebo group. The overall survival time showed a positive correlation with the Hb level (P = 0.000), and a negative correlation with the serum levels of IL-6 (P = 0.009).
  
  
  CONCLUSIONS
  rHuEPO increases Hb levels and survival time and reduces serum IL-6 and M-protein of the mice with multiple myeloma.
authors.affiliation: Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Mei-yu
authors.initials: MY
authors.lastname: Zhou
authors.forename: Liu
authors.initials: L
authors.lastname: Yu
authors.forename: Wen-tong
authors.initials: WT
authors.lastname: Meng
authors.forename: Cai-gang
authors.initials: CG
authors.lastname: Xu
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D007136:Immunoglobulins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000188:drug therapy*; D011897:Random Allocation; D011994:Recombinant Proteins
chemical_list: D006454:Hemoglobins; D007136:Immunoglobulins; D015850:Interleukin-6; C009823:M-proteins (Myeloma); D011994:Recombinant Proteins; D004921:Erythropoietin