title: [Comparison of the chemoimmunotherapeutic effect of doxorubicin and bafilomycin-A1 in mouse neuroblastoma cells].
abstract: The aim of this study was to compare the ability of the drugs doxorubicin and Bafilomycin-A1(Baf-A1)to promote an immune reaction following the induction of cell death in a mouse neuroblastoma model. Neuro-2a cells were cultured in medium containing doxorubicin or Baf-A1. Bone marrow-derived dendritic cells(BM-DCs)were co-cultured with neuro-2A cells that were grown in doxorubicin- or Baf-A1-containing media, and phagocytosis of neuro-2a cells by the BN-DCs was evaluated. Additionally, dead neuro-2a cells were co-cultured with CD8a + lymphocytes and BM-DCs, and the proliferation of CD8a + cells was evaluated. Interferon-g(IFN-g)production was used as an indexof the immune response. Dead neuro-2a cells treated with doxorubicin were phagocytosed effectively compared to the cells treated with Baf-A1. However, phagocytosis of cells treated with Baf-A1 was promoted after stimulation with CpG oligodeoxynucleotide (CpG-ODN). When CD8a + cells were co-cultured with BM-DCs and doxorubicin-treated neuro-2a cells, CD8a + lymphocyte proliferation was observed. There was no statistical difference in IFN-g secretion between the doxorubicin-treated and Baf-A1-treated cells. However, after stimulation by CpG-ODN, IFN-g production was more effectively observed in the Baf-A1-treated cells. Induction of cell death by doxorubicin or Baf-A1 could possibly enhance antitumor immunity in patients receiving chemotherapy for neuroblastoma. Selection of anti-tumor agents and stimulation of BM-DCs with a toll-like receptor (TLR) agonist is considered important in promoting antitumor activity after chemotherapy.
authors.affiliation: Dept. of Hepato-Biliary-Pancreatic and Pediatric Surgery,Saitama Medical Center, Saitama Medical University.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Inoue
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Setoyama
authors.forename: Akio
authors.initials: A
authors.lastname: Odaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D007167:Immunotherapy; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy
chemical_list: D016898:Interferon-alpha; D018942:Macrolides; D004317:Doxorubicin; C040929:bafilomycin A1