title: Recombinant hIFN-α2b-BCG inhibits tumor growth in a mouse model of bladder cancer.
abstract: Bacillus Calmette-Guérin (BCG) reduces the recurrence and progression of non-muscle invasive bladder cancer. The present study aimed to investigate the impact of a recombinant hIFN-α2b-secreting BCG (rBCG) on the mouse bladder MB49 cell line and an orthotopic mouse model of bladder cancer. MB49 cells were cultivated in the presence or absence of rBCG, BCG or BCG+hIFN-α2b. Cellular morphology and viability were assessed by microscopy and CCK-8 assay, respectively. Apoptosis was assessed by acridine orange, Hoechst 33258 staining and flow cytometry. MHC-I expression was assessed by flow cytometry. MB49 cells were transplanted into the bladders of C57BL/6 mice administered BCG, rBCG or BCG+hIFN-α2b. Local tissue Fas expression and T cell subsets were assessed by immunohistochemistry. Peripheral blood TNF-α and IL-12 levels were measured by ELISA, and circulating T lymphocyte subsets by flow cytometry. BCG, rBCG and BCG+hIFN-α2b increased the distortion and death of MB49 cells, yet rBCG reduced the proliferation and enhanced apoptosis most substantially. Apoptosis was increased after a 24-h co-culture with rBCG or BCG+hIFN-α2b. Mice administered rBCG survived longer than mice administered BCG (p<0.001), yet this result was not significantly different from mice administered BCG+hIFN-α2b. The average bladder weight was reduced by administration of rBCG (p<0.001). Fas expression and peripheral blood mTNF-α and mIL-12, cell counts of polymorphonuclear leukocytes, monocytes, T lymphocytes and CD4+/CD8+ ratios were significantly increased by all BCG treatments (p≤0.05), yet monocyte and T lymphocyte counts were higher in mice administered rBCG than in mice treated with BCG or BCG+hIFN-α2b (p=0.000). These results indicate that in an orthotopic murine bladder cancer model rBCG possesses superior antitumor activity to BCG+hIFN-α2b.
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Erlin
authors.initials: E
authors.lastname: Sun
authors.affiliation: Department of Gynaecology, Tianjin City Hospital for Gynaecology and Obstetrics, Tianjin 300100, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Mingde
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Nian
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Ruifa
authors.initials: R
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007372:Interferons