Therapeutic effect of recombinant Salmonella SGN1 on melanoma in mice and its mechanism of action
10.13200/j.cnki.cjb.004267
- VernacularTitle:重组沙门菌SGN1对小鼠黑色素瘤的治疗效果及其作用机制
- Author:
ZHENG Kexin
- Publication Type:Journal Article
- Keywords:
Melanoma;
Attenuated Salmonella;
Cell proliferation;
Tumor microenvironment;
T lymphocyte
- From:
Chinese Journal of Biologicals
2024;37(07):843-848+854
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect of recombinant Salmonella SGN1 on murine melanoma model and the action mechanism,and to provide reference for clinical treatment of melanoma with SGN1.Methods The recombinant Salmonella SGN1 and control strain VNP-V were co-cultured with mouse melanoma B16F10 cells,and the effect of SGN1 on the proliferation of B16F10 cells in vitro was detected by cell counting method. The B16F10 subcutaneous tumor transplantation model in mice was constructed. SGN1,VNP-V and PBS(control group)were injected into the tumor at a single dose,with five mice in each group,and the inhibitory effect of SGN1 on tumor growth was observed. The pathological changes of tumor tissues in mice were observed by HE staining. The distribution of SGN1 in tumor tissues was observed by plate counting. Flow cytometry was used to evaluate the proportion of infiltrating T lymphocyte subsets. The expression of T-cell marker CD3 was detected by immunofluorescence and immunohistochemical staining.Results Compared with the control group,recombinant Salmonella SGN1 significantly inhibited the proliferation of mouse melanoma B16F10 cells in vitro(t = 6. 935,P < 0. 01). In tumor-bearing mice,SGN1 was tumor-targeted and significantly inhibited the growth of B16F10 subcutaneous transplanted melanoma in mice(t = 7. 566,P < 0. 001). HE staining showed that SGN1 significantly induced the necrosis of subcutaneous transplanted melanoma cells in mice. The results of immunofluorescence,immunohistochemistry and flow cytometry confirmed that SGN1 significantly increased tumor-infiltrating CD3~+ T-cells(t = 11. 91,8. 873 and 5. 300,respectively,each P < 0. 01).Conclusion The recombinant Salmonella SGN1 can significantly inhibit the proliferation of B16F10 cells and exert anti-tumor effects by promoting tumor cell necrosis and elevating CD3~+ tumor-infiltrating T-cells,providing a theoretical basis for the clinical treatment of melanoma with SGN1
