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载吉西他滨的人骨髓间充质干细胞来源外泌体通过增强凋亡抑制胰腺癌细胞增殖

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

查看英文原题

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

PubMed 2024/09/15(内容时间) World J Gastrointest Oncol Q3 · IF 2.7(JCR 2025)

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研究概要

人骨髓 MSC 来源的 Exo-GEM 通过促进人胰腺癌细胞凋亡而对其具有强效细胞毒性,为改善治疗结局提供了一种有前景的药物递送系统。

中文摘要

胰腺癌仍是致死率最高的恶性肿瘤之一,有效治疗有限。化疗药物 gemcitabine(GEM)常用于胰腺癌临床治疗,但存在药物递送效率低和副作用显著等特点。本研究检验以下假设:负载 GEM 的人骨髓间充质干细胞(MSC)来源外泌体(Exo-GEM)可通过增强细胞凋亡,提高对人胰腺癌细胞的细胞毒性。

在体外研究 MSC 来源 Exo-GEM 对胰腺癌细胞的细胞毒性。

从 MSC 中分离外泌体,并通过透射电子显微镜和纳米颗粒跟踪分析进行表征。采用电穿孔、超声或孵育方式制备 Exo-GEM,并评估其载药效率。使用 MTT 和流式细胞术检测 Exo-GEM 或单独 GEM 对人胰腺癌 Panc-1 和 MiaPaca-2 细胞的细胞毒性。

分离所得外泌体的平均粒径为 76.7 nm。电穿孔和超声法对 GEM 的包封率与载药效率相近,且均显著优于孵育法。Exo-GEM 对胰腺癌细胞的细胞毒性强于游离 GEM;0.02 M Exo-GEM 显著降低 Panc-1 和 MiaPaca-2 细胞的存活率。此外,Exo-GEM 增强了 GEM 在两种细胞系中诱导凋亡的频率。

人骨髓 MSC 来源 Exo-GEM 可通过增强细胞凋亡,对人胰腺癌细胞产生强效细胞毒性,有望成为改善治疗结局的药物递送系统。

展开英文摘要原文

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 .

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.

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 M 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.

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.

论文信息

作者
Tang ZG、Chen TM、Lu Y、Wang Z、Wang XC、Kong Y
第一作者单位
Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, Guangdong Province, China.China
通讯作者单位
Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518000, Guangdong Province, China. yi.kong@siat.ac.cn.China
期刊
World journal of gastrointestinal oncology2024 Sep 15
原文标识
PubMed 39350998 · DOI 10.4251/wjgo.v16.i9.4006