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Antitumor Effect of Cycle Inhibiting Factor Expression in Colon Cancer via Salmonella VNP20009
Liang Liu1,2, Junhua Zhang1,2, Mingqiang Gu3
1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Background:
Colon cancer is one of the major causes of morbidity and mortality worldwide. Cycle inhibiting factors (Cifs) have been shown to deamidate Nedd8, resulting in cell cycle arrest.
Objective:
To determine the antitumor effect of Cifs on colon cancer by using attenuated Salmonella typhimurium VNP20009.
Methods:
The VNP-SOPE2-cif and VNP-SOPE2-cif-C/A plasmids were transfected into attenuated Salmonella typhimurium VNP20009. The efficiency and specificity of the Cif promoter were validated in colon cancer SW480 cell lines. Western blotting was subsequently performed to evaluate cell cycle regulators, including P21, P27 and Wee1. In vivo, the antitumor effect of VNP20009 was evaluated in a colon cancer xenograft model.
Results:
Firstly, VNP-SOPE2-cif and VNP-SOPE2-cif-C/A were selectively expressed both in the bacterial and colon cancer cells. Cif expression in SW480 cells via the VNP tumor-targeted expression system induced the accumulation of Wee1, p21 and p27 expression. Moreover, tumor growth was significantly inhibited in the mice with VNP-SOPE2-cif compared to the mice with VNP with the empty construct.
Conclusion:
These results suggest that Cif gene delivered by VNP20009 is a promising approach for the treatment of colon cancer.
Insights
Cycle inhibiting factors (Cifs) delivered by attenuated Salmonella typhimurium VNP20009 show promise for colon cancer treatment. This approach effectively inhibits tumor growth by inducing cell cycle arrest in cancer cells.
Area of Science:
- Oncology
- Microbiology
- Molecular Biology
Background:
- Colon cancer poses a significant global health burden, contributing to substantial morbidity and mortality.
- Cycle inhibiting factors (Cifs) are known to induce cell cycle arrest by deamidating Nedd8.
Purpose of the Study:
- To investigate the potential antitumor effects of Cifs on colon cancer.
- To utilize attenuated Salmonella typhimurium VNP20009 as a delivery system for Cif genes.
Main Methods:
- Engineered Salmonella typhimurium VNP20009 to carry Cif genes (VNP-SOPE2-cif and VNP-SOPE2-cif-C/A).
- Validated Cif promoter efficiency in colon cancer SW480 cell lines.
- Assessed cell cycle regulators (P21, P27, Wee1) via Western blotting.
- Evaluated in vivo antitumor activity in a colon cancer xenograft model.
Main Results:
- Selective expression of Cif genes was confirmed in both bacterial and colon cancer cells.
- Cif expression in SW480 cells led to increased levels of Wee1, P21, and P27.
- Significant inhibition of tumor growth was observed in mice treated with VNP-SOPE2-cif compared to controls.
Conclusions:
- The Cif gene, delivered by VNP20009, demonstrates a promising therapeutic strategy for colon cancer.
- This bacterial-mediated gene delivery system effectively targets and inhibits colon cancer progression.
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