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百里醌增加SW-480结肠癌细胞对5-氟尿嘧啶的敏感性。

Thymoquinone Increases the Sensitivity of SW-480 Colon Cancer Cells to 5-Fluorouracil.

作者信息

Zeinali Nima, Mahmoudzadeh Vahid, Anarjani Alireza, Ebrahimnejad Mohammad, Yousefi Bahman, Valizadeh Amir

机构信息

Molecular Medicine Research Center Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Clinical Biochemistry and Laboratory Medicine Faculty of Medicine Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Biomed Res Int. 2024 Jul 9;2024:6231095. doi: 10.1155/2024/6231095. eCollection 2024.

Abstract

Studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in diverse malignancies, such as colorectal cancer. Nevertheless, the precise mechanisms of TQ-mediated anticancer properties are not yet fully elucidated. The present study has been designed to scrutinize the impact of TQ on 5-fluorouracil (5-FU)-mediated apoptosis in SW-480 cells. SW-480 cells were treated with TQ, 5-FU, and a combination of TQ + 5-FU. MTT assay was employed to assess cell viability. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to evaluate apoptotic markers comprising Bcl-2, Bax, and caspase-9 expression levels. The -H2AX protein expression was assessed by western blotting, and Annexin V flow cytometry was implemented to determine the apoptosis rate. 5-FU significantly reversed the cell proliferation in a dose-dependent circumstance. The concurrent administration of TQ and 5-FU led to a substantial inhibition of cell growth in comparison to single treatments ( < 0.05). TQ also facilitated apoptosis via upregulating Bax and caspase-9 proapoptotic markers and suppressing antiapoptotic mediators, like Bcl-2. In addition, TQ augmented 5-FU-induced apoptosis in SW-480 cells. 5-FU, combined with TQ, increased the protein expression of -H2AX in SW-480 cells compared with groups treated with TQ and 5-FU alone. The present study's findings unveil the significance of TQ as a potential therapeutic substance in colorectal cancer, particularly through enhancing 5-FU-induced apoptosis.

摘要

研究集中在天然多酚百里醌(TQ)对多种恶性肿瘤(如结直肠癌)的治疗潜力上。然而,TQ介导的抗癌特性的确切机制尚未完全阐明。本研究旨在探讨TQ对SW - 480细胞中5 - 氟尿嘧啶(5 - FU)介导的细胞凋亡的影响。用TQ、5 - FU以及TQ + 5 - FU组合处理SW - 480细胞。采用MTT法评估细胞活力。应用定量实时聚合酶链反应(qRT - PCR)评估包括Bcl - 2、Bax和caspase - 9表达水平在内的凋亡标志物。通过蛋白质印迹法评估γ - H2AX蛋白表达,并采用膜联蛋白V流式细胞术测定细胞凋亡率。5 - FU在剂量依赖性情况下显著抑制细胞增殖。与单一处理相比,TQ和5 - FU联合给药导致细胞生长受到显著抑制(P < 0.05)。TQ还通过上调促凋亡标志物Bax和caspase - 9以及抑制抗凋亡介质(如Bcl - 2)促进细胞凋亡。此外,TQ增强了5 - FU诱导的SW - 480细胞凋亡。与单独用TQ和5 - FU处理的组相比,5 - FU与TQ联合处理增加了SW - 480细胞中γ - H2AX的蛋白表达。本研究结果揭示了TQ作为结直肠癌潜在治疗物质的重要性,特别是通过增强5 - FU诱导的细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/11251801/fa4a93c4cca1/BMRI2024-6231095.001.jpg

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