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凋亡和自噬在叶酸诱导的人乳腺癌细胞体外细胞毒性中的作用。

Role of apoptosis and autophagy in folic acid-induced cytotoxicity of human breast cancer cells in vitro.

机构信息

Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.

Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri, 38039, Turkey.

出版信息

Fundam Clin Pharmacol. 2024 Feb;38(1):126-138. doi: 10.1111/fcp.12948. Epub 2023 Aug 16.

DOI:10.1111/fcp.12948
PMID:37587691
Abstract

Obstacles to the successful treatment of breast cancer patients with chemotherapeutic agents can be overcome with effective new strategies. It is still unclear how folic acid affects the onset and spread of breast cancer. The purpose of this study was to determine how folic acid affected the apoptotic and autophagic pathways of the breast cancer cell lines MCF-7 and MDA-MB-231. In the present study, folic acid was applied to MCF-7 and MDA-MB-231 breast cancer cell lines at different concentrations and for different durations. MTT analysis was used to investigate cytotoxic activity. All groups underwent the Tunel staining procedure to identify apoptosis and the immunofluorescence staining approach to identify the autophagic pathway. 24-hour folic acid values were accepted as the most appropriate cytotoxic dose. In MCF-7, cell cycle arrest was observed in the S phase and MDA-MB-231 G1/G0 phases. When apoptotic TUNEL staining was evaluated in both cell lines, folic acid significantly increased apoptosis. While a significant difference was observed between the groups in terms of Beclin 1 immunoreactivity in the MDA-MB-231 cell line, there was no significant difference in the MCF-7 cell line. In addition, statistical significance was not observed LC3 immunoreactivity in both cell lines. In the study, it was observed that folic acid induced autophagy at the initial stage in the MDA-MB-231 cell line but had no inductive effect in the MCF-7 cell line. In conclusion, our findings showed that folic acid has a potential cytotoxic and therapeutic effect on MCF-7 and MDA-MB-231 breast cancer cell lines.

摘要

用有效的新策略可以克服乳腺癌患者用化疗药物治疗的障碍。目前尚不清楚叶酸如何影响乳腺癌的发病和扩散。本研究的目的是确定叶酸如何影响 MCF-7 和 MDA-MB-231 乳腺癌细胞系的凋亡和自噬途径。在本研究中,不同浓度和不同时间向 MCF-7 和 MDA-MB-231 乳腺癌细胞系应用叶酸。MTT 分析用于研究细胞毒性活性。所有组均接受 Tunel 染色程序以鉴定凋亡和免疫荧光染色方法以鉴定自噬途径。24 小时叶酸值被认为是最合适的细胞毒性剂量。在 MCF-7 中,观察到细胞周期停滞在 S 期和 MDA-MB-231 G1/G0 期。当在两种细胞系中评估凋亡 TUNEL 染色时,叶酸显着增加了凋亡。虽然在 MDA-MB-231 细胞系中贝林 1 免疫反应性方面观察到组间有显着差异,但在 MCF-7 细胞系中没有显着差异。此外,在两种细胞系中均未观察到 LC3 免疫反应性的统计学意义。在研究中,观察到叶酸在 MDA-MB-231 细胞系中在初始阶段诱导自噬,但在 MCF-7 细胞系中没有诱导作用。总之,我们的研究结果表明,叶酸对 MCF-7 和 MDA-MB-231 乳腺癌细胞系具有潜在的细胞毒性和治疗作用。

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