Tumor-targeting engineered probiotic Escherichia coli Nissle 1917 inhibits colorectal tumorigenesis and modulates gut microbiota homeostasis in mice
DC Field | Value | Language |
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dc.contributor.author | Tang, Haibo | - |
dc.contributor.author | Zhou, Tuoyu | - |
dc.contributor.author | Jin, Weilin | - |
dc.contributor.author | Zong, Simin | - |
dc.contributor.author | Mamtimin, Tursunay | - |
dc.contributor.author | Salama, El-Sayed | - |
dc.contributor.author | Jeon, Byong-Hun | - |
dc.contributor.author | Liu, Pu | - |
dc.contributor.author | Han, Huawen | - |
dc.contributor.author | Li, Xiangkai | - |
dc.date.accessioned | 2023-07-05T04:20:54Z | - |
dc.date.available | 2023-07-05T04:20:54Z | - |
dc.date.created | 2023-05-16 | - |
dc.date.issued | 2023-07 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/186373 | - |
dc.description.abstract | Aims: Preliminary studies have identified the use of probiotics as a potential treatment strategy against colorectal cancer (CRC). However, natural probiotics lack direct tumor-targeting and tumor-killing activity in the intestine. This study aimed to construct a tumor-targeting engineered probiotic to combat CRC. Main methods: Standard adhesion assay was performed to analyze the adherence ability of tumor-binding protein HlpA to CT26 cells. CCK-8 assay, Hoechst 33258 staining and flow cytometry analysis were used for examining cytotoxicity of tumoricidal protein azurin toward CT26 cells. An engineered probiotic Ep-AH harboring azurin and hlpA genes was developed using Escherichia coli Nissle 1917 (EcN) chassis. Antitumor effects of Ep-AH were evaluated in the azoxymethane (AOM) and dextran sodium sulfate salt (DSS)-induced CRC mice. Moreover, analysis of gut microbiota was conducted via fecal 16S rRNA gene sequencing and shotgun metagenomic sequencing. Key findings: Azurin caused a dose-dependent increase of apoptosis in CT26 cells. Ep-AH treatment reversed weight loss (p < 0.001), fecal occult blood (p < 0.01), and shortening of colon length (p < 0.001) than model group, as well as reducing tumorigenesis by 36 % (p < 0.001). Both Ep-H and Ep-A (EcN expressing HlpA or azurin) were less effective than Ep-AH. Furthermore, Ep-AH enriched the members of beneficial bacteria (e.g., Blautia and Bifidobacterium) and reversed abnormal changes of genes associated with several metabolic pathways (e.g., lipopolysaccharide biosynthesis). Significance: These results demonstrated that Ep-AH had excellent therapeutic benefits on cancer remission and gut microbiota modulation. Our study provides an effective strategy for anti-CRC treatment. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.title | Tumor-targeting engineered probiotic Escherichia coli Nissle 1917 inhibits colorectal tumorigenesis and modulates gut microbiota homeostasis in mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jeon, Byong-Hun | - |
dc.identifier.doi | 10.1016/j.lfs.2023.121709 | - |
dc.identifier.scopusid | 2-s2.0-85153796434 | - |
dc.identifier.wosid | 000990814100001 | - |
dc.identifier.bibliographicCitation | LIFE SCIENCES, v.324, pp.1 - 13 | - |
dc.relation.isPartOf | LIFE SCIENCES | - |
dc.citation.title | LIFE SCIENCES | - |
dc.citation.volume | 324 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 13 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | ALIGNMENT | - |
dc.subject.keywordPlus | ADHESION | - |
dc.subject.keywordPlus | AZURIN | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordAuthor | Engineered probiotic | - |
dc.subject.keywordAuthor | Escherichia coli Nissle 1917 | - |
dc.subject.keywordAuthor | AOM | - |
dc.subject.keywordAuthor | DSS model | - |
dc.subject.keywordAuthor | Tumor-targeting treatment | - |
dc.subject.keywordAuthor | Gut microbiota | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0024320523003430?via%3Dihub | - |
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