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Antitumor Effect of Cycle Inhibiting Factor Expression in Colon Cancer via Salmonella VNP20009.
- Source :
-
Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2020; Vol. 20 (14), pp. 1722-1727. - Publication Year :
- 2020
-
Abstract
- 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.<br />Objective: To determine the antitumor effect of Cifs on colon cancer by using attenuated Salmonella typhimurium VNP20009.<br />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.<br />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.<br />Conclusion: These results suggest that Cif gene delivered by VNP20009 is a promising approach for the treatment of colon cancer.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Bacterial Vaccines chemistry
Cell Line, Tumor
Colonic Neoplasms genetics
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Mice
Molecular Structure
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Bacterial Vaccines pharmacology
Colonic Neoplasms drug therapy
Escherichia coli Proteins genetics
Salmonella typhimurium chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1875-5992
- Volume :
- 20
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Anti-cancer agents in medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32324525
- Full Text :
- https://doi.org/10.2174/1871520620666200423080622