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同源肿瘤来源的外泌体致敏的鼠骨髓基质细胞抑制肝癌细胞增殖。

Murine bone marrow stromal cells pulsed with homologous tumor-derived exosomes inhibit proliferation of liver cancer cells.

机构信息

Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Medical Oncology, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, China.

出版信息

Clin Transl Oncol. 2012 Oct;14(10):764-73. doi: 10.1007/s12094-012-0860-9. Epub 2012 Jul 27.

Abstract

BACKGROUND

Increasing evidence shows that bone marrow stromal cells (BMSCs) have antitumor activities both in vitro and in animal models. Further studies fleshed out the supportive data that the antitumor activity of BMSCs could be markedly enhanced by cytokines such as IL-2 and IFN-β (interferon). However, powerful strategies to activate BMSCs other than by genetically engineering interventions are still required.

METHODS

In this study, new methods of generating antitumor activities of murine marrow-originated MSCs pulsed with homologous tumor-derived exosomes (TEX) were explored to yield potent immune effectors against hepatocellular carcinoma cells in vitro.

RESULTS

The results showed that BMSCs pulsed with exosomes and IFN-γ exhibited increased migration ability with a result of 163.22 ± 26.90 versus 129.89 ± 29.28 cells/HP by transwell determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma cells line H(22) cells by exosomes pulsed BMSCs was significantly increased by 41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that the cell cycle of H(22) cells was arrested in G(0)/G(1) phase. Meanwhile, western blot analysis showed that PCNA protein expression in the supernatant of H(22) cells was significantly decreased.

CONCLUSIONS

This study demonstrated that BMSCs pulsed with TEX could enhance its antitumor activities, which might be regarded as a novel promising antitumor treatment.

摘要

背景

越来越多的证据表明,骨髓基质细胞(BMSCs)在体外和动物模型中均具有抗肿瘤活性。进一步的研究充实了数据,即细胞因子如白细胞介素 2(IL-2)和干扰素-β(IFN-β)可显著增强 BMSCs 的抗肿瘤活性。然而,除了基因工程干预之外,还需要强大的策略来激活 BMSCs。

方法

在这项研究中,探索了用同源肿瘤衍生的外泌体(TEX)脉冲处理鼠源性骨髓来源的 MSC 以产生抗肿瘤活性的新方法,以在体外生成针对肝细胞癌细胞的有效免疫效应物。

结果

结果表明,用外泌体和 IFN-γ 脉冲处理的 BMSCs 迁移能力增加,穿过小室的细胞数为 163.22 ± 26.90 个/高倍视野,而未经处理的细胞数为 129.89 ± 29.28 个/高倍视野(p < 0.05)。与对照组相比,用外泌体脉冲处理的 BMSCs 对同源肝细胞癌细胞系 H(22)细胞的抑制作用显著增加了 41.9%(p < 0.05),流式细胞术分析表明 H(22)细胞的细胞周期被阻滞在 G0/G1 期。同时,Western blot 分析表明,H(22)细胞上清液中的 PCNA 蛋白表达显著降低。

结论

这项研究表明,用 TEX 脉冲处理的 BMSCs 可增强其抗肿瘤活性,这可能被视为一种有前途的新型抗肿瘤治疗方法。

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