Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis.

IF 2.5 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

World Journal of Gastrointestinal Oncology Pub Date : 2024-09-15 DOI:10.4251/wjgo.v16.i9.4006

Zu-Gui Tang, Tie-Mei Chen, Yi Lu, Zhe Wang, Xi-Cheng Wang, Yi Kong

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引用次数: 0

Abstract

Background: Pancreatic cancer remains one of the most lethal malignancies, and has limited effective treatment. Gemcitabine (GEM), a chemotherapeutic agent, is commonly used for clinical treatment of pancreatic cancer, but it has characteristics of low drug delivery efficiency and significant side effects. The study tested the hypothesis that human bone marrow mesenchymal stem cell (MSC)-derived exosomes loaded with GEM (Exo-GEM) would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.

Aim: To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.

Methods: Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis. Exo-GEM through electroporation, sonication, or incubation, and the loading efficiency was evaluated. The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.

Results: The isolated exosomes had an average size of 76.7 nm. The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation. The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02 μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells. Moreover, Exo-GEM enhanced the frequency of GEM-induced apoptosis in both cell lines.

Conclusion: Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis, offering a promising drug delivery system for improving therapeutic outcomes.

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含有吉西他滨的人骨髓间充质干细胞衍生外泌体通过增强细胞凋亡抑制胰腺癌细胞增殖。

背景：胰腺癌仍是致死率最高的恶性肿瘤之一，且有效治疗手段有限。吉西他滨（GEM）是一种化疗药物，常用于胰腺癌的临床治疗，但它具有给药效率低、副作用大的特点。该研究测试了一种假设，即人骨髓间充质干细胞（MSC）衍生的外泌体（Exo-GEM）负载有GEM，会通过增强胰腺癌细胞的凋亡而对人胰腺癌细胞具有更高的细胞毒性：方法：从间充质干细胞中分离出外泌体，并通过透射电子显微镜和纳米粒子追踪分析对其进行表征。方法：从间充质干细胞中分离出外泌体，并通过透射电子显微镜和纳米颗粒追踪分析对其进行表征。通过 MTT 和流式细胞术检测评估了 Exo-GEM 或单独 GEM 对人胰腺癌 Panc-1 和 MiaPaca-2 细胞的细胞毒性：结果：分离出的外泌体平均大小为 76.7 nm。结果：分离出的外泌体平均大小为 76.7 nm，电穿孔法和超声法对 GEM 的包封效果和负载效率相似，且明显优于孵育法。Exo-GEM 对胰腺癌细胞的细胞毒性强于游离 GEM，用 0.02 μM Exo-GEM 处理可显著降低 Panc-1 和 MiaPaca-2 细胞的存活率。此外，Exo-GEM 还能提高 GEM 诱导的两种细胞系的凋亡频率：结论：人骨髓间充质干细胞衍生的Exo-GEM通过增强细胞凋亡对人胰腺癌细胞具有强大的细胞毒性，为改善治疗效果提供了一种前景广阔的给药系统。

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来源期刊

World Journal of Gastrointestinal Oncology Medicine-Gastroenterology

CiteScore

4.20

自引率

3.30%

发文量

1082

期刊介绍： The World Journal of Gastrointestinal Oncology (WJGO) is a leading academic journal devoted to reporting the latest, cutting-edge research progress and findings of basic research and clinical practice in the field of gastrointestinal oncology.