Combination of Methotrexate and Resveratrol Reduces Pro-Inflammatory Chemokines in Human THP-1 Cells.

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2024-11-02 eCollection Date: 2024-01-01 DOI:10.2147/JIR.S482503
Moonerah M Al-Nasser, Mashael J Al-Saeedi, Saltana A Alhowaiti, Zakia Shinwari, Fatimah S Alhamlan, Hani Alothaid, Saad Alkahtani, Ahmed A Al-Qahtani
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引用次数: 0

Abstract

Introduction: Methotrexate (MTX) is a widely used anti-metabolite drug in cancer therapy, but its efficacy is often hindered by reactive oxygen species (ROS)-induced cellular toxicity. Resveratrol, a natural polyphenol, possesses antioxidant and anticancer properties. Therefore, this in vitro study aimed to investigate the synergistic anti-proliferative and anti-inflammatory effects of MTX and resveratrol in human THP-1 cells.

Methods: THP-1 cells were differentiated into macrophage-like cells using phorbol 12-myristate 13-acetate. In vitro experiments assessed the impact of various concentrations of MTX and resveratrol on cell viability and proliferation using the MTT assay. Concentration-effect curves were generated to elucidate their relationship. Gene expression was analyzed by RT-qPCR, while chemokine expression was measured via ELISA. Phagocytic and migratory activities were also evaluated.

Results: Differentiated THP-1 cells were treated with MTX and resveratrol and stimulated with dimethyl sulfoxide (DMSO) and lipopolysaccharide (LPS) as inflammatory stimuli. The combination of MTX and resveratrol exhibited an anti-proliferative effect in THP-1 cells (p = 0.03). The concentration-effect curve revealed IC50 values of 49.15 µg at 24 hours (R = 0.8236) and 2.029e-005 µg at 48 hours (R = 0.97) for MTX, and 20.17 µg at 48 hours (R = 1.000) and 55.38 µg at 96 hours (R = 0.9666) for resveratrol. Co-treatment with MTX and resveratrol significantly reduced mRNA and chemokine expression of CCL2, CCL3, CCL4, CCL5, and CXCL10 (p < 0.05). Moreover, decreased phagocytic and migratory activities were confirmed by phagocytosis and migration assays (p < 0.05).

Conclusion: The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.

甲氨蝶呤和白藜芦醇合用可减少人 THP-1 细胞中的促炎趋化因子
导言:甲氨蝶呤(MTX)是一种广泛应用于癌症治疗的抗代谢药物,但其疗效往往受到活性氧(ROS)引起的细胞毒性的影响。白藜芦醇是一种天然多酚,具有抗氧化和抗癌特性。因此,本体外研究旨在探讨 MTX 和白藜芦醇在人 THP-1 细胞中的协同抗增殖和抗炎作用:方法:使用 12-肉豆蔻酸 13-乙酸磷脂将 THP-1 细胞分化成巨噬细胞样细胞。体外实验采用 MTT 法评估了不同浓度的 MTX 和白藜芦醇对细胞活力和增殖的影响。生成浓度-效应曲线以阐明它们之间的关系。基因表达通过 RT-qPCR 进行分析,趋化因子表达则通过 ELISA 进行测量。此外,还对吞噬和迁移活动进行了评估:用 MTX 和白藜芦醇处理分化的 THP-1 细胞,并用二甲基亚砜(DMSO)和脂多糖(LPS)作为炎症刺激。MTX 和白藜芦醇的组合对 THP-1 细胞具有抗增殖作用(p = 0.03)。浓度-效应曲线显示,MTX 24 小时的 IC50 值为 49.15 微克(R = 0.8236),48 小时为 2.029e-005 微克(R = 0.97);白藜芦醇 48 小时的 IC50 值为 20.17 微克(R = 1.000),96 小时为 55.38 微克(R = 0.9666)。联合使用 MTX 和白藜芦醇可显著降低 CCL2、CCL3、CCL4、CCL5 和 CXCL10 的 mRNA 和趋化因子表达(p < 0.05)。此外,吞噬和迁移试验证实了吞噬和迁移活性的降低(p < 0.05):结论:MTX 和白藜芦醇联合使用可有效减轻 THP-1 细胞的促炎活性,这一点可通过下调 mRNA 和趋化因子的表达得到证实。这些研究结果表明,MTX 和白藜芦醇的协同作用有望提高癌症治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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