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研究贝林司他通过 Wnt、Notch 和 Hedgehog 信号通路对 MCF-7 乳腺癌干细胞的作用。

Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway.

机构信息

From the Department of Medical Biology (Tuncer, Kurar), Meram Faculty of Medicine, Necmettin Erbakan University, from the Department of Medical Biology (Tuncer); and from the Department of Medical Genetics (Duran), Faculty of Medicine, KTO Karatay University, Konya, Turkey.

出版信息

Saudi Med J. 2024 Feb;45(2):121-127. doi: 10.15537/smj.2024.45.2.20230478.

Abstract

OBJECTIVES

To evaluate belinostat's (PXD101) activity on MCF-7 breast cancer stem cells (CSCs) via Wnt, Notch, and Hedgehog.

METHODS

This research study was carried out at the Department of Medical Biology, Necmettin Erbakan University, Konya, Turkey, from June 2017 to July 2019. The effect of PXD101 on MCF-7 cell viability was determined by cell proliferation kit (XTT). Following belinostat treatment, CD44+/CD24- MCF-7 CSCs were isolated by FACS. Ribonucleic acid isolation and copy-deoxyribonucleic acid synthesis were carried out using HEK-293 cells, MCF-7 cells, and MCF-7 CSCs. Expression changes of metastasis-related genes, Wnt, Hedgehog, Notch, and stem cell markers were analysed by quantitative polymerase chain reaction. The IC50 in MCF-7 cancer cells was 5 μM for 48 hours. The FACS analysis indicated that 2% of the MCF-7 cancer cells were CSCs. Following belinostat treatment, the MCF-7 cell count decreased by 44%, and the MCF-7 CD44+/CD24- CSC count decreased by 66%.

RESULTS

Belinostat treatment reduced the expression of metastasis, Wnt, Notch, Hedgehog, and stem cell marker genes.

CONCLUSION

Belinostat has a potential effect on the differentiation and self-renewal of breast CSCs.

摘要

目的

通过 Wnt、Notch 和 Hedgehog 通路评估贝林司他(PXD101)对 MCF-7 乳腺癌干细胞(CSCs)的作用。

方法

本研究于 2017 年 6 月至 2019 年 7 月在土耳其 Necmettin Erbakan 大学医学生物学系进行。通过细胞增殖试剂盒(XTT)测定 PXD101 对 MCF-7 细胞活力的影响。经贝林司他处理后,通过流式细胞术分离 CD44+/CD24-MCF-7 CSCs。使用 HEK-293 细胞、MCF-7 细胞和 MCF-7 CSCs 进行核糖核酸分离和脱氧核糖核酸合成。通过定量聚合酶链反应分析转移相关基因、Wnt、Hedgehog、Notch 和干细胞标志物的表达变化。MCF-7 癌细胞的 IC50 为 5 μM,作用 48 小时。流式细胞术分析表明,2%的 MCF-7 癌细胞为 CSCs。经贝林司他处理后,MCF-7 细胞计数减少了 44%,MCF-7 CD44+/CD24-MCF-7 CSC 计数减少了 66%。

结果

贝林司他处理降低了转移、Wnt、Notch、Hedgehog 和干细胞标志物基因的表达。

结论

贝林司他对乳腺 CSCs 的分化和自我更新具有潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c791/11115415/d45f263e9be0/SaudiMedJ-45-2-121_1.jpg

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