title: Oral administration of immunopotentiator from Pantoea agglomerans 1 (IP-PA1) improves the survival of B16 melanoma-inoculated model mice.
abstract: To investigate the usefulness of the immunopotentiator from Pantoea agglomerans 1 (IP-PA1) as a supportive drug in melanoma therapy, we analyzed the immunological effects of IP-PA1 on melanoma-inoculated model mice. Oral administration of IP-PA1 increased the serum levels of tumor necrosis factor (TNF)-α at 2 h after the administration and interferon (IFN)-γ and IL-12 at 12 h after the administration in naïve BALB/cCrSlc mice as evaluated by ELISA. IP-PA1 did not affect the proliferation of melanoma cells directly determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Combinatory treatment of IP-PA1 with doxorubicin for 9 days increased the serum levels of IFN-γ and IL-12 by 71.0 and 15.3%, respectively, compared to the treatment of doxorubicin alone in melanoma-bearing C57BL/6NCrSlc mice as evaluated by ELISA. It also increased the proportion of natural killer (NK) cells and the ratio of CD4(+) to CD8(+) T cells in the spleen from 6.1 ± 0.3 to 7.4 ± 0.5% and from 1.25 ± 0.03 to 1.38 ± 0.04, respectively, compared to the treatment of doxorubicin alone as analyzed by flow cytometry. The mean survival period of melanoma-bearing, doxorubicin treated mice was prolonged from 31.4 ± 7.1 to 35.3 ± 8.4, 51.1 ± 5.4, and 45.0 ± 8.4 days by combinatory treatment of IP-PA1 at the daily doses of 0.1, 0.5, and 1 mg/kg, respectively. In conclusion, the results of the present study suggest the usefulness of IP-PA1 as a supportive drug in melanoma therapy.
authors.affiliation: Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hebishima
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Gen-ichiro
authors.initials: G
authors.lastname: Soma
authors.forename: Chie
authors.initials: C
authors.lastname: Kohchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirota
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D020636:Pantoea / Q000737:chemistry*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D004317:Doxorubicin; D007371:Interferon-gamma