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间充质干细胞通过 GSK-3α/β 和 ERK1/2 信号通路促进 Molt-4 白血病细胞中 Caspase 的表达作为一种治疗策略。

Mesenchymal Stem Cells Promote Caspase Expression in Molt-4 Leukemia Cells GSK-3α/Β and ERK1/2 Signaling Pathways as a Therapeutic Strategy.

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Institute of Cell Biology, Medical University of Innsbruck, Biocenter, Innsbruck, Austria.

出版信息

Curr Gene Ther. 2021;21(1):81-88. doi: 10.2174/1566523220666201005111126.

Abstract

BACKGROUND

Mesenchymal stem cells (MSCs) are considered an interesting tool in cell therapy due to their unique features such as self-renewal, multi-potency, and pluripotency. The multifunctional properties of these cells are being investigated in many studies. The current research examined the influence of MSCs on the Molt-4 cell line as acute lymphoblastic leukemia (ALL) cells.

METHODS

MSCs were cultured, characterized, and co-cultured with Molt-4 cells in a trans-well system. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to western blotting for protein expression assessment. Telomerase activity as well as cell senescence, were investigated by PCR-ELISA TRAP assay and β-galactosidase activity measurement, respectively.

RESULTS

It was found that MSCs resulted in a significant increase in the pro-caspase-8 and cleaved-caspase 8 and 9 expression levels. Furthermore, protein expression levels of GSK-3α/β and ERK1/2 were significantly decreased. The results also showed that MSCs caused significant decreases and increases in telomerase and β-galactosidase enzyme activity of Molt-4 cells, respectively.

CONCLUSION

It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis and cell senescence via caspase-8, 9 cascade and GSK-3α/β and ERK1/2 signaling pathways.

摘要

背景

间充质干细胞(MSCs)因其自我更新、多能性和多能性等独特特性,被认为是细胞治疗中的一种有趣工具。这些细胞的多功能特性正在许多研究中进行研究。目前的研究检查了 MSCs 对急性淋巴细胞白血病(ALL)细胞 Molt-4 细胞系的影响。

方法

培养、表征 MSC,并在 Trans-well 系统中与 Molt-4 细胞共培养。然后,在第 7 天收集单独培养的 Molt-4 和与 MSC 共培养的 Molt-4(10:1),并进行 Western blot 以评估蛋白表达。通过 PCR-ELISA TRAP 测定和β-半乳糖苷酶活性测定分别研究端粒酶活性和细胞衰老。

结果

发现 MSCs 导致前胱天蛋白酶-8 和裂解胱天蛋白酶 8 和 9 的表达水平显著增加。此外,GSK-3α/β 和 ERK1/2 的蛋白表达水平显著降低。结果还表明,MSCs 导致 Molt-4 细胞的端粒酶和β-半乳糖苷酶酶活性分别显著降低和增加。

结论

结论是与 Molt-4 细胞共培养的 MSC 可能通过胱天蛋白酶-8、9 级联和 GSK-3α/β 和 ERK1/2 信号通路参与促进 Molt-4 细胞凋亡和细胞衰老。

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