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左旋肉碱对MDA-MB-231乳腺癌细胞系CD44癌干细胞的影响作为抗癌治疗的研究。

Investigation of L-carnitine effects on CD44 cancer stem cells from MDA-MB-231 breast cancer cell line as anti-cancer therapy.

作者信息

Farahzadi Raheleh, Sanaat Zohreh, Movassaghpour-Akbari Ali Akbar, Fathi Ezzatollah, Montazersaheb Soheila

机构信息

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

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

出版信息

Regen Ther. 2023 Jul 14;24:219-226. doi: 10.1016/j.reth.2023.06.014. eCollection 2023 Dec.

Abstract

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells, capable of metastasis, recurrence, and drug resistance in breast cancer patients. Therefore, targeting BCSCs appears to be a promising strategy for the treatment and prevention of breast cancer metastasis. Mounting evidence supports the fact that carnitine, a potent antioxidant, modulates various mechanisms by enhancing cellular respiration, inducing apoptosis, and reducing proliferation and inflammatory responses in tumor cells. The objective of this study was to investigate the impact of L-carnitine (LC) on the rate of proliferation and induction of apoptosis in CD44 CSCs. To achieve this, the CD44 cells were enriched using the Magnetic-activated cell sorting (MACS) isolation method, followed by treatment with LC at various concentrations. Flow cytometry analysis was used to determine cell apoptosis and proliferation, and western blotting was performed to detect the expression levels of proteins. Treatment with LC resulted in a significant decrease in the levels of p-JAK2, p-STAT3, Leptin receptor, and components of the leptin pathway. Moreover, CD44 CSCs-treated cells with LC exhibited a reduction in the proliferation rate, accompanied by an increase in the percentage of apoptotic cells. Hence, it was concluded that LC could potentially influence the proliferation and apoptosis of CD44 CSC by modulating the expression levels of specific protein.

摘要

乳腺癌干细胞(BCSCs)是乳腺癌细胞中的一个小亚群,能够导致乳腺癌患者发生转移、复发和产生耐药性。因此,靶向BCSCs似乎是治疗和预防乳腺癌转移的一种有前景的策略。越来越多的证据支持这样一个事实,即肉碱作为一种有效的抗氧化剂,通过增强细胞呼吸、诱导细胞凋亡以及减少肿瘤细胞的增殖和炎症反应来调节各种机制。本研究的目的是探讨左旋肉碱(LC)对CD44癌干细胞增殖率和凋亡诱导的影响。为了实现这一目标,使用磁激活细胞分选(MACS)分离方法富集CD44细胞,然后用不同浓度的LC进行处理。采用流式细胞术分析来确定细胞凋亡和增殖情况,并进行蛋白质印迹法检测蛋白质的表达水平。LC处理导致p-JAK2、p-STAT3、瘦素受体和瘦素信号通路成分的水平显著降低。此外,用LC处理的CD44癌干细胞显示增殖率降低,同时凋亡细胞百分比增加。因此,得出的结论是,LC可能通过调节特定蛋白质的表达水平来影响CD44癌干细胞的增殖和凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f88/10384609/e6faa310b68d/gr1.jpg

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