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潜在益生菌 L. fermentum 和 L. plantarum 与 5-氟尿嘧啶联合对结直肠癌细胞的抗癌作用。

The anticancer effect of potential probiotic L. fermentum and L. plantarum in combination with 5-fluorouracil on colorectal cancer cells.

机构信息

Department of Microbiology, College of Sciences, Agriculture and Modern Technology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.

Department of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

World J Microbiol Biotechnol. 2024 Mar 22;40(5):139. doi: 10.1007/s11274-024-03929-9.

DOI:10.1007/s11274-024-03929-9
PMID:38514489
Abstract

5-Fluorouracil (5-FU) is an effective chemotherapy drug in the treatment of colorectal cancer (CRC). However, auxiliary or alternative therapies must be sought due to its resistance and potential side effects. Certain probiotic metabolites exhibit anticancer properties. In this study evaluated the anticancer and potential therapeutic activities of cell extracts potential probiotic strains, Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from the mule milk and the standard probiotic strain Lacticaseibacillus rhamnosus GG (LGG) against the human colon cancer cell line (HT-29) and the normal cell line (HEK-293) alone or in combination with 5-FU. In this study, L. plantarum and L. fermentum, which were isolated from mule milk, were identified using biochemical and molecular methods. Their probiotic properties were investigated in vitro and compared with the standard probiotic strain of the species L. rhamnosus GG. The MTT assay, acridine orange/ethidium bromide (AO/EB) fluorescent staining, and flow cytometry were employed to measure the viability of cell lines, cell apoptosis, and production rates of Th17 cytokines, respectively. The results demonstrated that the combination of lactobacilli cell extracts and 5-FU decreased cell viability and induced apoptosis in HT-29 cells. Furthermore, this combination protected HEK-293 cells from the cytotoxic effects of 5-FU, enhancing their viability and reducing apoptosis. Moreover, the combination treatment led to an increase in the levels of IL-17A, IFN-γ, and TNF-α, which can enhance anti-tumor immunity. In conclusion, the cell extracts of the lactobacilli strains probably can act as a potential complementary anticancer therapy.

摘要

5-氟尿嘧啶(5-FU)是治疗结直肠癌(CRC)的有效化疗药物。然而,由于其耐药性和潜在的副作用,必须寻求辅助或替代疗法。某些益生菌代谢物具有抗癌特性。在这项研究中,评估了从骡奶中分离出的潜在益生菌菌株Limosilactobacillus fermentum 和 Lactiplantibacillus plantarum 的细胞提取物以及标准益生菌菌株Lacticaseibacillus rhamnosus GG(LGG)单独或与 5-FU 联合对人结肠癌细胞系(HT-29)和正常细胞系(HEK-293)的抗癌和潜在治疗活性。在这项研究中,使用生化和分子方法鉴定了从骡奶中分离出的植物乳杆菌和发酵乳杆菌。体外研究了它们的益生菌特性,并与该属的标准益生菌菌株鼠李糖乳杆菌 GG 进行了比较。MTT 测定法、吖啶橙/溴化乙锭(AO/EB)荧光染色和流式细胞术分别用于测量细胞系的活力、细胞凋亡和 Th17 细胞因子的产生率。结果表明,乳酸菌细胞提取物与 5-FU 的联合使用降低了 HT-29 细胞的活力并诱导其凋亡。此外,这种联合保护了 HEK-293 细胞免受 5-FU 的细胞毒性作用,提高了其活力并减少了凋亡。此外,联合治疗导致 IL-17A、IFN-γ 和 TNF-α 的水平增加,这可以增强抗肿瘤免疫。总之,乳酸菌菌株的细胞提取物可能可以作为一种潜在的互补抗癌疗法。

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