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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.

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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