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.
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 × 10(9), 3.2- .0 × 10(8), 6.4-8.0 × 10(7) 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.
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
T
Li
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.
Li
L
Yang
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.
Sheng-Jun
SJ
Fu
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.
Er-Long
EL
Xiao
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.
Xuan
X
Yuan
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.
Jian-Zhong
JZ
Lu
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.
Bao-Liang
BL
Ma
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.
Ting-Kai
TK
Shi
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. erywzp@lzu.edu.cn.
Zhi-Ping
ZP
Wang
D000818:Animals; D016516:CD4-CD8 Ratio; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D001749:Urinary Bladder Neoplasms / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C000603452:mannosesensitive haemagglutinin, Pseudomonas aeruginosa; D036781:Fimbriae Proteins; D007371:Interferon-gamma
Bladder tumor; Cytokines; Mice; Microvessel density; Pseudomonas aeruginosa; Vascular endothelial growth factor