The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People's Republic of China.
The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, People's Republic of China.
Int J Nanomedicine. 2023 May 9;18:2431-2446. doi: 10.2147/IJN.S394133. eCollection 2023.
Pancreatic adenocarcinoma (PAAD) presents an extremely high morbidity and mortality rate. Broccoli has excellent anti-cancer properties. However, the dosage and serious side effects still limit the application of broccoli and its derivatives for cancer therapy. Recently, extracellular vesicles (EVs) derived from plants are emerging as novel therapeutic agents. Thus, we conducted this study to determine the effectiveness of EVs isolated from Se-riched broccoli (Se-BDEVs) and conventional broccoli (cBDEVs) for the treatment of PAAD.
In this study, we first isolated Se-BDEVs and cBDEVs by a differential centrifugation method, and characterized them by using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Then, miRNA-seq was combined with target genes prediction, and functional enrichment analysis to reveal the potential function of Se-BDEVs and cBDEVs. Finally, the functional verification was conducted in PANC-1 cells.
Se-BDEVs and cBDEVs exhibited similar characteristics in size and morphology. Subsequent miRNA-seq revealed the expression of miRNAs in Se-BDEVs and cBDEVs. Using a combination of miRNA target prediction and KEGG functional analysis, we found miRNAs in Se-BDEVs and cBDEVs may play an important role in treating pancreatic cancer. Indeed, our in vitro study showed that Se-BDEVs had greater anti-PAAD potency than cBDEVs due to increased bna-miR167a_R-2 (miR167a) expression. Transfection with miR167a mimics significantly induced apoptosis of PANC-1 cells. Mechanistically, further bioinformatics analysis showed that , which is involved in the PI3K-AKT pathway, is the key target gene of miR167a.
This study highlights the role of miR167a transported by Se-BDEVs which could be a new tool for counteracting tumorigenesis.
胰腺导管腺癌（PAAD）具有极高的发病率和死亡率。西兰花具有出色的抗癌特性。然而，剂量和严重的副作用仍然限制了西兰花及其衍生物在癌症治疗中的应用。最近，植物来源的细胞外囊泡（EVs）作为新型治疗剂崭露头角。因此，我们进行了这项研究，以确定富含硒的西兰花（Se-BDEVs）和普通西兰花（cBDEVs）衍生的 EVs 治疗 PAAD 的效果。
在这项研究中，我们首先通过差速离心法分离 Se-BDEVs 和 cBDEVs，并通过纳米颗粒跟踪分析（NTA）和透射电子显微镜（TEM）对其进行表征。然后，miRNA-seq 结合靶基因预测和功能富集分析，揭示 Se-BDEVs 和 cBDEVs 的潜在功能。最后，在 PANC-1 细胞中进行功能验证。
Se-BDEVs 和 cBDEVs 在大小和形态上表现出相似的特征。随后的 miRNA-seq 显示了 Se-BDEVs 和 cBDEVs 中 miRNAs 的表达。通过 miRNA 靶标预测和 KEGG 功能分析的结合，我们发现 Se-BDEVs 和 cBDEVs 中的 miRNAs 可能在治疗胰腺癌方面发挥重要作用。事实上，我们的体外研究表明，由于 bna-miR167a_R-2（miR167a）表达增加，Se-BDEVs 对 PAAD 的抑制作用强于 cBDEVs。转染 miR167a 模拟物可显著诱导 PANC-1 细胞凋亡。在机制上，进一步的生物信息学分析表明，PI3K-AKT 通路中的关键靶基因是 miR167a。
本研究强调了 Se-BDEVs 转运的 miR167a 的作用，这可能成为对抗肿瘤发生的新工具。
