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

甲氨蝶呤和白藜芦醇的组合可降低人类 THP-1 细胞中的促炎趋化因子

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作者:Moonerah M Al-Nasser, Mashael J Al-Saeedi, Saltana A Alhowaiti, Zakia Shinwari, Fatimah S Alhamlan, Hani Alothaid, Saad Alkahtani, Ahmed A Al-Qahtani

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.

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).

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