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工程益生菌大肠杆菌 Nissle 1917 释放 PTEN 以改善肿瘤微环境并抑制肿瘤生长。

Engineered probiotic E.coli Nissle 1917 for release PTEN to improve the tumor microenvironment and suppress tumor growth.

机构信息

State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life Science, Hunan Normal University, No. 36 Lushan Street, Changsha, 410081, People's Republic of China.

出版信息

Biotechnol Lett. 2024 Dec;46(6):1237-1247. doi: 10.1007/s10529-024-03536-6. Epub 2024 Sep 27.

DOI:10.1007/s10529-024-03536-6
PMID:39331305
Abstract

The cancer is one of the diseases of serious threat to people's health and life nowadays. But heterogeneity, drug resistance and treatment side effects of cancer, traditional treatments still have limitations. Tumor-targeting probiotics with a well-established Biosafety and efficient targeting as a delivery vectors to deliver anticancer genes or antitumor drugs to tumor microenvironment has attracted much attention in cancer therapies. In this study, E.coil Nissle 1917 (EcN) was utilized to deliver eukaryotic anti-tumor protein PTEN to tumor microenvironment and suppress tumor growth. Therefore, the EcN (PTEN) was developed. Our results demonstrated that EcN (PTEN) could colonize the tumor site accurately and inhibit the growth of colorectal cancer cells in tumor-bearing mice. It is worth noting that the tumor microenvironment of the treated mice showed significant recruitment of and M1 macrophages, neutrophils and T lymphocytes. No toxicity was observed in the normal tissues during the experiments. This research show the probiotic EcN(PTEN) holds the promise of becoming a powerful weapon against cancer and expected to provide more effective treatments for cancer patients.

摘要

癌症是当今严重威胁人类健康和生命的疾病之一。但癌症的异质性、耐药性和治疗副作用,使得传统治疗方法仍存在局限性。肿瘤靶向益生菌具有良好的生物安全性和高效靶向性,可作为递送载体将抗癌基因或抗肿瘤药物递送到肿瘤微环境中,在癌症治疗中引起了广泛关注。在本研究中,利用大肠杆菌 Nissle 1917(EcN)将真核抗肿瘤蛋白 PTEN 递送到肿瘤微环境中,抑制肿瘤生长。因此,开发了 EcN(PTEN)。我们的结果表明,EcN(PTEN)可以准确定植于肿瘤部位,并抑制荷瘤小鼠结直肠癌细胞的生长。值得注意的是,治疗小鼠的肿瘤微环境中出现了大量 M1 巨噬细胞、中性粒细胞和 T 淋巴细胞的募集。在实验过程中,正常组织没有观察到毒性。这项研究表明,益生菌 EcN(PTEN)有望成为对抗癌症的有力武器,并为癌症患者提供更有效的治疗方法。

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Engineered probiotic E.coli Nissle 1917 for release PTEN to improve the tumor microenvironment and suppress tumor growth.工程益生菌大肠杆菌 Nissle 1917 释放 PTEN 以改善肿瘤微环境并抑制肿瘤生长。
Biotechnol Lett. 2024 Dec;46(6):1237-1247. doi: 10.1007/s10529-024-03536-6. Epub 2024 Sep 27.
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Intestinal probiotics Nissle 1917 as a targeted vehicle for delivery of p53 and Tum-5 to solid tumors for cancer therapy.肠道益生菌Nissle 1917作为将p53和Tum-5递送至实体瘤用于癌症治疗的靶向载体。
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Tumor-targeting engineered probiotic Escherichia coli Nissle 1917 inhibits colorectal tumorigenesis and modulates gut microbiota homeostasis in mice.肿瘤靶向工程益生菌大肠杆菌 Nissle 1917 抑制结直肠肿瘤发生,并调节小鼠肠道微生物组稳态。
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本文引用的文献

1
Tumor-targeting engineered probiotic Escherichia coli Nissle 1917 inhibits colorectal tumorigenesis and modulates gut microbiota homeostasis in mice.肿瘤靶向工程益生菌大肠杆菌 Nissle 1917 抑制结直肠肿瘤发生,并调节小鼠肠道微生物组稳态。
Life Sci. 2023 Jul 1;324:121709. doi: 10.1016/j.lfs.2023.121709. Epub 2023 Apr 24.
2
Bacteria-Mediated Tumor Therapy via Photothermally-Programmed Cytolysin A Expression.细菌介导的肿瘤治疗通过光控细胞溶素 A 表达实现。
Small. 2021 Oct;17(40):e2102932. doi: 10.1002/smll.202102932. Epub 2021 Sep 1.
3
Anti-cancer properties of Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways.
1917 株大肠杆菌通过调控 Bax/Bcl-xL 和 AKT/PTEN 信号通路对 HT-29 结肠癌细胞的抗癌特性
Iran J Basic Med Sci. 2020 Jul;23(7):886-893. doi: 10.22038/ijbms.2020.43016.10115.
4
Intestinal probiotics Nissle 1917 as a targeted vehicle for delivery of p53 and Tum-5 to solid tumors for cancer therapy.肠道益生菌Nissle 1917作为将p53和Tum-5递送至实体瘤用于癌症治疗的靶向载体。
J Biol Eng. 2019 Jun 28;13:58. doi: 10.1186/s13036-019-0189-9. eCollection 2019.
5
Combination Therapy of TGF-β Blockade and Commensal-derived Probiotics Provides Enhanced Antitumor Immune Response and Tumor Suppression.联合使用 TGF-β 阻断剂和共生益生菌可增强抗肿瘤免疫反应和抑制肿瘤生长。
Theranostics. 2019 May 31;9(14):4115-4129. doi: 10.7150/thno.35131. eCollection 2019.
6
PTEN: Tumor Suppressor and Metabolic Regulator.PTEN:肿瘤抑制因子与代谢调节因子
Front Endocrinol (Lausanne). 2018 Jul 9;9:338. doi: 10.3389/fendo.2018.00338. eCollection 2018.
7
Nissle 1917 engineered to express Tum-5 can restrain murine melanoma growth.经过基因工程改造以表达Tum-5的Nissle 1917能够抑制小鼠黑色素瘤的生长。
Oncotarget. 2017 Aug 24;8(49):85772-85782. doi: 10.18632/oncotarget.20486. eCollection 2017 Oct 17.
8
Use of Bacteria in Cancer Therapy.细菌在癌症治疗中的应用。
Recent Results Cancer Res. 2016;209:111-121. doi: 10.1007/978-3-319-42934-2_8.
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Outer Membrane Vesicles from the Probiotic Escherichia coli Nissle 1917 and the Commensal ECOR12 Enter Intestinal Epithelial Cells via Clathrin-Dependent Endocytosis and Elicit Differential Effects on DNA Damage.来自益生菌大肠杆菌Nissle 1917和共生菌ECOR12的外膜囊泡通过网格蛋白依赖的内吞作用进入肠道上皮细胞,并对DNA损伤产生不同影响。
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