摘要
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 13-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 （P〈O.05）. The co-stimulation-related molecules on DCs were comparable to those stimulated by LPS. Immunohistochemical examinations demonstrated the repression of 13-catenin in B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse transcription PCR revealed that HVJ-E induced a remarkable infiltration of CDllc 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 13-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. Conclusion 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.
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 13-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 （P〈O.05）. The co-stimulation-related molecules on DCs were comparable to those stimulated by LPS. Immunohistochemical examinations demonstrated the repression of 13-catenin in B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse transcription PCR revealed that HVJ-E induced a remarkable infiltration of CDllc 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 13-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. Conclusion 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.
基金
supported by a grant from the National High Technology Research and Development Program of China(2012AA101302)
Natural Science Foundation of Jiangsu Province(BK2011049)
Jiangsu"333"projects in Jiangsu province(BK201140032)
