Department of Pathogenic Biology, School of Basic Medicine, Jinzhou Medical University, 121001 Jinzhou, Liaoning, China.
Experimental Teaching Center of Basic Medicine, Jinzhou Medical University, 121001 Jinzhou, Liaoning, China.
Front Biosci (Landmark Ed). 2024 Jun 28;29(7):241. doi: 10.31083/j.fbl2907241.
The involvement of gut microbiota in carcinogenesis has gradually been highlighted in past decades. Bacteria could play its role by the secretion of extracellular vesicles (EVs); however, interrelationship between bacterial EVs and hepatocellular carcinoma (HCC) development has not been investigated much.
Diethylnitrosamine (DEN) was utilized to produce HCC model in mice, of which fecal was collected for detecting () with real-time polymerase chain reaction (PCR). EV isolated from (-EV) with ultracentrifugation were stained with PKH26 to investigate the cellular uptake of murine hepatocytes (AML12). After treatment with -EV, TGF-β1-induced AML12 cells were subjected to morphological observation, fibrosis- and apoptosis-related marker detection with western blot, apoptotic ratio and reactive oxygen species (ROS) level analysis with flow cytometry, and oxidative stress biomarker assessment with enzyme-linked immunosorbent assay (ELISA); meanwhile, animal studies including liver function, tumor formation rate, and histological analysis, were also performed to investigate the role of -EV in the fibrosis, apoptosis, oxidative stress, and carcinogenesis of the liver .
The levels of were significantly reduced in HCC model mice. -EV could enter AML12 cells and effectively attenuate TGF-β1-induced fibrosis, apoptosis, and oxidative stress in AML12 cells. studies showed that -EV administration alleviated DEN-induced liver fibrosis, apoptosis, and oxidative stress at the early stage. Moreover, -EV administration also effectively reduced the tumor formation rate and liver function injury in DEN-induced mice and down-regulated TGF-β1 expression and Smad3 phosphorylation of mouse liver.
-EVs protect hepatocytes against fibrosis, apoptosis, and oxidative damage, which exert a potential of preventing HCC development.
在过去几十年中，肠道微生物群在癌症发生中的作用逐渐受到重视。细菌可以通过分泌细胞外囊泡（EVs）发挥作用；然而，细菌 EVs 与肝细胞癌（HCC）发展之间的相互关系尚未得到充分研究。
利用二乙基亚硝胺（DEN）在小鼠中产生 HCC 模型，收集粪便用于实时聚合酶链反应（PCR）检测（）。用超速离心法从（-EV）中分离 EV 并用 PKH26 染色，以研究鼠肝细胞（AML12）的细胞摄取。用 -EV 处理后，用 TGF-β1 诱导 AML12 细胞进行形态学观察，用 Western blot 检测纤维化和凋亡相关标志物，用流式细胞术检测凋亡率和活性氧（ROS）水平，并通过酶联免疫吸附试验（ELISA）评估氧化应激生物标志物；同时，进行动物研究，包括肝功能、肿瘤形成率和组织学分析，以研究 -EV 在肝脏纤维化、凋亡、氧化应激和癌变中的作用。
HCC 模型小鼠中（）水平显著降低。-EV 可以进入 AML12 细胞，并有效减轻 TGF-β1 诱导的 AML12 细胞纤维化、凋亡和氧化应激。研究表明，-EV 给药可在 DEN 诱导的早期阶段减轻肝纤维化、凋亡和氧化应激。此外，-EV 给药还可有效降低 DEN 诱导的小鼠肿瘤形成率和肝功能损伤，并下调 TGF-β1 表达和 Smad3 磷酸化的小鼠肝。
-EVs 可保护肝细胞免受纤维化、凋亡和氧化损伤，具有预防 HCC 发展的潜力。
