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IL15 修饰的 NK-92 细胞释放的外泌体对 HL-60 细胞系凋亡的影响

英文原题:The Effects of Released Exosomes from NK-92 Cells with IL15 on the Apoptosis of HL-60 Cell Line.

查看英文原题

The Effects of Released Exosomes from NK-92 Cells with IL15 on the Apoptosis of HL-60 Cell Line.

PubMed 2025/04/01(内容时间) Int J Hematol Oncol Stem Cell Res

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中文摘要

大多数癌症通过化疗和放疗进行治疗。然而,由于癌细胞能够逃避免疫检测,这些方法存在局限性,促使研究人员探索免疫疗法等替代方案。尽管如此,癌细胞可以削弱免疫反应,因此需要改进免疫治疗方法。外泌体是微小的细胞来源纳米颗粒,反映其来源细胞的特征。自然杀伤NK细胞产生包含穿孔素、颗粒酶、Fas-L等的外泌体。这些外泌体的小尺寸、与肿瘤的邻近性以及稳定性使其易于被癌细胞吸收。本研究表明,IL-15影响NK来源的外泌体,增强其杀死癌细胞的能力。

向NK-92细胞培养物中加入100纳克/毫升的IL-15后,将细胞孵育48小时。然后通过超速离心法从处理过和未处理的NK-92细胞系中分离外泌体。分离后,将两组不同浓度的外泌体加入HL-60细胞中进行处理。24小时后,通过Annexin-V法评估凋亡率。

BCA测试中光吸收增加,以及Western blotting测试中CD63和CD81条带增厚,表明向源细胞加入IL-15后外泌体产量更高。t检验的低p值表明,来自刺激后NK细胞的外泌体比对照组的外泌体更具细胞毒性。此外,双因素ANOVA证实了每个浓度下对照组和治疗组之间的差异,Welch's t检验证明ANOVA测试中的所有差异均显著。

本文提供的证据表明,与未受刺激的NK细胞来源的外泌体相比,IL-15诱导的NK细胞来源的外泌体不仅数量增加,而且对白血病细胞表现出显著的细胞毒性。

展开英文摘要原文

Background : Most cancers are treated through chemotherapy and radiotherapy.

However, these methods have limitations due to cancer cells evading immune detection, prompting researchers to explore alternatives such as immunotherapy. Nonetheless, cancer cells can weaken the immune response, necessitating improvements in immunotherapy methods. Exosomes, tiny cell-derived nanoparticles, reflect the traits of their originating cells. Natural Killer NK cells produce exosomes comprising perforin, granzyme, Fas-L, etc. The small size, proximity to tumors, and stability of these exosomes enable easy absorption by cancer cells.

This study demonstrates that IL-15 impacts NK-derived exosomes, enhancing their ability to kill cancer cells. Materials and Methods: With the addition of 100 nanograms per milliliter of IL-15 to NK-92 cell culture, the cells are incubated for 48 hours. Exosomes are then isolated from treated and non-treated NK-92 cell lines through the ultracentrifuge method. After isolation, different concentrations of exosomes from both groups are added to HL-60 cells for treatment.

After 24 hours, the apoptosis rate is assessed through the Annexin-V method. Results: Increased light absorption in the BCA test, along with thicker bands of CD63 and CD81 in the Western blotting test, indicates a higher yield of exosomes after adding IL-15 to the source cells. The low p-value from the t-test demonstrates that exosomes derived from stimulated NK cells are more cytotoxic than those from the control group.

Further, two-way ANOVA confirms differences between the control and treatment groups at each concentration, and Welch's t-test proves that all differences in the ANOVA test are significant. Conclusion: This article presents evidence that exosomes obtained from IL-15-induced NK cells not only increase in quantity but also demonstrate significant cytotoxicity against leukemic cells compared to exosomes obtained from non-stimulated NK cells.

论文信息

作者
Abbasi S、Movassaghpour A、Soleimani M、Asghari Molabashi Z
第一作者单位
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Iran
通讯作者单位
Department of Plant Molecular Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.Iran
期刊
International journal of hematology-oncology and stem cell research2025 Apr 1
原文标识
PubMed 40852695 · DOI 10.18502/ijhoscr.v19i2.18550