基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
渥曼青霉素浸渍间充质干细胞条件培养基经 PI3K/Akt/mTOR 通路增强乳腺癌细胞抗增殖效应
英文原题：Impregnation of mesenchymal stem cell conditioned media with wortmannin enhanced its antiproliferative effect in breast cancer cells via PI3K/Akt/mTOR pathway.
查看英文原题
Impregnation of mesenchymal stem cell conditioned media with wortmannin enhanced its antiproliferative effect in breast cancer cells via PI3K/Akt/mTOR pathway.
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研究概要
这些发现揭示了 pan-PI3K/Akt/mTOR 抑制剂与 MSC 来源的-CM 联合使用通过下调 PI3K/AKT/mTOR 信号通路在乳腺癌中具有有前景的抗增殖和抗转移效果。需要进一步研究以验证这种化学再生策略在癌症治疗中的应用。
研究思路结论见上方概要
背景
源自间充质干细胞的条件培养基（MSC-CM）被认为是一种有前景的无细胞再生疗法替代方案。据推测，MSC-CM与抗癌药物的协同作用可能提高其对癌细胞的抗增殖和抗转移效果。在此，我们将MSC-CM与Wortmannin（一种pan-PI3K/Akt/mTOR抑制剂）浸渗结合，并研究了它们对乳腺癌细胞的联合效应。
方法
为探索这一点，对 luminal-A 型乳腺癌细胞（MCF-7）的细胞毒性、凋亡及自噬潜能进行了评估。
结果
我们发现，将 MCF-7 与含 Wort 的条件培养基共孵育可诱导凋亡和自噬介导的细胞死亡，而延长暴露则导致大量坏死性细胞死亡。MSC-CM 的参与有效降低了在 Wort 处理细胞中观察到的 Wortmannin IC50。此外，载有 Wort 的条件培养基诱导核 DNA 片段化并减少体外细胞迁移。这些发现与 Wort 依赖性的细胞活力降低、磷酸化 Akt 和 mTOR 蛋白的形成、mRNA 表达减少以及磷脂酰肌醇-4,5-二磷酸 3-激酶催化结构域（PI3K-Ca）表达下调相关。
展开英文摘要原文
MATERIALS AND METHODS
To explore this, the cytotoxic, apoptotic, and autophagic potentials were assessed in luminal-A breast cancer cells (MCF-7).
RESULTS
We found that incubation of MCF-7 to Wort-containing-CM induced apoptosis- and autophagy-mediated cell death, meanwhile prolonged exposure caused massive necrotic cell death. The involvement of MSC-CM effectively reduced Wortmannin IC50 observed in Wort-treated cells. Also, Wort-loaded-CM induced nuclear DNA fragmentation and reduced in vitro cell migration. These findings were associated with a Wort-dependent reduction in cell viability, the formation of the phosphorylated Akt and mTOR proteins, reduced the expression of mRNA, and downregulated the expression of the catalytic domain of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K-Ca).
CONCLUSION
These findings revealed the promising antiproliferative and antimetastasis effects of combining pan-PI3K/Akt/mTOR inhibitors with MSC-derived-CM in breast cancer via the downregulation of PI3K/AKT/mTOR signaling pathways. Further studies are required to validate this chem-regenerative strategy in cancer treatment.
论文信息
- 作者
- Ismail DF、El-Keey MM、Elgendy SM、Hessien M
- 第一作者单位
- Molecular Cell Biology Unit, Division of Biochemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt.Egypt
- 通讯作者单位
- Molecular Cell Biology Unit, Division of Biochemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt. Mohamed.Hussien1@science.tanta.edu.eg.Egypt
- 期刊
- BMC research notes2025 Mar 4
- 原文标识
- PubMed 40038752 · DOI 10.1186/s13104-025-07124-3
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