Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis

J Transl Med. 2013 Sep 5;11:205. doi: 10.1186/1479-5876-11-205.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Genotype
  • Immunity / immunology*
  • Interleukin-6 / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred BALB C
  • Sendai virus / genetics*
  • Sendai virus / physiology*
  • Sendai virus / radiation effects
  • Survival Analysis
  • Ultraviolet Rays
  • Virus Inactivation* / radiation effects

Substances

  • Interleukin-6