title: Inactivated Sendai virus suppresses murine melanoma growth by inducing host immune responses and down-regulating β-catenin expression.
abstract: OBJECTIVE
  This paper aims to investigate the anti-tumor mechanism of inactivated Sendai virus (Hemagglutinating virus of Japan envelope, HVJ-E) for murine melanoma (B16F10).
  
  
  METHODS
  The murine dendritic cells (DCs) were treated with HVJ-E, and then the cytokines secreted from DCs and costimulation-related molecules on DCs were measured. Meanwhile, the expression of β-catenin in HVJ-E treated murine melanoma cells was detected. In addition, HVJ-E was intratumorally injected into the melanoma on C57BL/6 mice, and the immune cells, CTL response and tumor volume were analyzed.
  
  
  RESULTS
  HVJ-E injected into B16F10 melanoma obviously inhibited the growth of the tumor and prolonged the survival time of the tumor-bearing mice. Profiles of cytokines secreted by dendritic cells (DCs) after HVJ-E stimulation showed that the number of cytokines released was significantly higher than that elicited by PBS (1P<0.05). The co-stimulation-related molecules on DCs were comparable to those stimulated by LPS. Immunohistochemical examinations demonstrated the repression of β-catenin in B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse transcription PCR revealed that HVJ-E induced a remarkable infiltration of CD11c positive cells, chemokine ligand 10 (CXCL10) molecules, interleukin-2 (IL-2) molecule, CD4(+) and CD8(+) T cells into HVJ-E injected tumors. Furthermore, the mRNA expression level of β-catenin in the HVJ-E injected tumors was also down-regulated. In addition, B16F10-specific CTLs were induced significantly after HVJ-E was injected into the tumor-bearing mice.
  
  
  CONCLUSIONS
  This is the first report to show the effective inhibition of melanoma tumors by HVJ-E alone and the mechanism through which it induces antitumor immune responses and regulates important signal pathways for melanoma invasion. Therefore, HVJ-E shows its prospect as a novel therapeutic for melanoma therapy.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China. zquan@yzu.edu.cn
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Yuan
authors.forename: Guo Qin
authors.initials: GQ
authors.lastname: Zhai
authors.forename: Shan Yuan
authors.initials: SY
authors.lastname: Zhu
authors.forename: Zheng Feng
authors.initials: ZF
authors.lastname: Xue
authors.forename: Hong Fei
authors.initials: HF
authors.lastname: Zhu
authors.forename: Xiang Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology / Q000821:virology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000502:physiology*; D038301:Virus Inactivation; D014779:Virus Replication; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051176:beta Catenin