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Subcutaneous Injections of the Mannose-Sensitive Hemagglutination Pilus Strain of Pseudomonas aeruginosa Stimulate Host Immunity, Reduce Bladder Cancer Size and Improve Tumor Survival in Mice

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Abstract

We wished to evaluate the effects of Pseudomonas aeruginosa (mannose-sensitive hemagglutination pilus strain, PA-MSHA) as an immunostimulating and anti-tumor agent for treatment of bladder cancer. Immunostimulating effects were assessed by the in vitro proliferation assay of murine splenic lymphocytes. Anti-tumor effects were studied in a subcutaneous tumor model established in female C57BL/6 mice using the MB49 bladder cell line. These mice received subcutaneous injections of normal saline (control group) or PA-MSHA (high, medium, or low dose, respectively, 1.6–2.0 × 109, 3.2– .0 × 108, 6.4–8.0 × 107 CFU/ml) twice a week for 3 weeks. Mice survival, tumor volume, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), serum levels of TNF-α and IFN-γ, and blood CD4+ /CD8+ counts were the study outcomes. We observed that PA-MSHA promoted the growth of splenic lymphocytes in vitro. In the murine tumor model, PA-MSHA prolonged mice survival and reduced tumor growth. Furthermore, VEGF and MVD were also diminished by PA-MSHA. Mice that received high and medium dose of PA-MSHA had significantly higher serum levels of IFN-γ and TNF-α (days 21 and 28), and higher levels of CD4+ /CD8+ cells (days 21 and 28). In conclusion, PA-MSHA exerts beneficial effects on increasing proliferation of murine splenic lymphocytes in vitro and inhibits the growth of bladder tumor in a murine model. Therefore, PA-MSHA may be useful an immunostimulating and anti-tumor agent for bladder cancer therapy.

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Abbreviations

P. aeruginosa :

Pseudomonas aeruginosa

VEGF:

Vascular endothelial growth factor

MVD:

Microvessel density

TURBT:

Transurethral resection of bladder tumor

TCC:

Transitional cell carcinoma cell

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Acknowledgments

This study was supported by the Central University basic business expense special fund (lzujbky-2011-142).

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    Authors and Affiliations

    1. Institute of Urology, Department of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, , Lanzhou University Second Hospital, 82 Cui YingMen Street, Lanzhou, 730030, Gansu, China

      Tao Li, Li Yang, Sheng-jun Fu, Er-long Xiao, Xuan Yuan, Jian-zhong Lu, Bao-liang Ma, Ting-kai Shi & Zhi-ping Wang

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    1. Tao Li
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    Correspondence to Zhi-ping Wang.

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    Tao Li and Li Yang have contributed equally to this study and should be considered co-first authors.

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    Li, T., Yang, L., Fu, Sj. et al. Subcutaneous Injections of the Mannose-Sensitive Hemagglutination Pilus Strain of Pseudomonas aeruginosa Stimulate Host Immunity, Reduce Bladder Cancer Size and Improve Tumor Survival in Mice. Cell Biochem Biophys 73, 245–252 (2015). https://doi.org/10.1007/s12013-015-0611-y

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