title: Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis.
abstract: BACKGROUND
  Ultraviolet-inactivated, replication-defective Sendai virus particles (Z strain) have displayed antitumor effect through enhancing the immune responses or inducing apoptosis in a variety of carcinomas. Sendai virus strain Tianjin was isolated from the lungs of marmoset and proved to be a novel genotype of Sendai virus. In this study, we explored the antitumor effect and its mechanism of ultraviolet-inactivated, replication-defective Sendai virus strain Tianjin (UV-Tianjin) in mice bearing CT26 colon carcinoma.
  
  
  METHODS
  Three injections of UV-Tianjin were delivered into CT26 tumors growing on the back of BALB/c mice. Tumor size was measured in a blinded manner and survival rate of mice was calculated. In order to make clear antitumor mechanism of UV-Tianjin, the maturation and interleukin-6 (IL-6) release from murine myeloid dendritic cells (DCs) was examined by flow cytometry or ELISA assay after induced by UV-Tianjin and compared with those of live virus. Moreover, real-time RT-PCR and immunohistochemistry was performed to identify whether UV-Tianjin could induce infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay was done to observe the apoptosis of CT26 tumor cells after UV-Tianjin injection.
  
  
  RESULTS
  In animal model, UV-Tianjin could obviously inhibit the growth of CT26 tumors and prolong the survival of the tumor-bearing mice compared with control group (P < 0.01). In vitro murine DCs stimulated by UV-Tianjin underwent dose-dependent maturation, similar to that elicited by live virus. And the secretion amount of IL-6 from DCs induced by UV-Tianjin was a little lower than that released in the presence of live virus. Real-time RT-PCR and immunohistochemistry revealed that UV-Tianjin induced a remarkable infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay showed that the apoptosis index of tumor tissues injected with UV-Tianjin was significantly higher than that of control group (P < 0.01).
  
  
  CONCLUSIONS
  Our results have demonstrated that UV-Tianjin alone could inhibit the growth of CT26 tumor in mice through enhancing host antitumor immunity and inducing apoptosis of tumor cells. Therefore, UV-Tianjin shows its prospect as a novel drug for carcinoma therapy.
authors.affiliation: Department of Microbiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China. htang2002@yahoo.com.
authors.forename: Liying
authors.initials: L
authors.lastname: Shi
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zhong
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Geng
authors.forename: Jianmin
authors.initials: J
authors.lastname: He
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sheng
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005838:Genotype; D007109:Immunity / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D029082:Sendai virus / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D016019:Survival Analysis; D014466:Ultraviolet Rays; D038301:Virus Inactivation / Q000528:radiation effects
chemical_list: D015850:Interleukin-6