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: Takehisa Hebishima, Yasunobu Matsumoto, Gen Watanabe, Gen-ichiro Soma, Chie Kohchi, Kazuyoshi Taya, Yoshihiro Hayashi, Yoshikazu Hirota
• Journal: Experimental animals (Exp Anim) Vol. 60 Issue 2 Pg. 101-9 ( 2011) ISSN: 1881-7122 [Electronic] Japan
• PMID: 21512265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Doxorubicin
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage, therapeutic use)
• Animals
• CD4-CD8 Ratio
• Cell Proliferation (drug effects)
• Doxorubicin (therapeutic use)
• Female
• Flow Cytometry
• Interferon-gamma (blood)
• Interleukin-12 (blood)
• Killer Cells, Natural (immunology)
• Lipopolysaccharides (administration & dosage, therapeutic use)
• Melanoma, Experimental (drug therapy, immunology, mortality)
• Mice
• Mice, Inbred C57BL
• Pantoea (chemistry)
• Skin Neoplasms (drug therapy, immunology, mortality)
• Spleen (immunology)
• Tumor Necrosis Factor-alpha (blood)