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

Journal of Translational Medicine

Hua Tang¹  Mingwei Sheng²  Zhe Han¹  Jianmin He¹  Peng Geng¹  Mei Li¹  Qiping Zhong¹  Jun Chen¹  Liying Shi¹ 

[1] Department of Microbiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China;Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China

关键词: Apoptosis;    Dendritic cells;    Antitumor immunity;    Murine colon carcinoma;    Sendai virus strain Tianjin;   

Others  :  826714
DOI  :  10.1186/1479-5876-11-205

 received in 2013-06-18, accepted in 2013-09-02,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Shi et al.; licensee BioMed Central Ltd.

【 图 表 】

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