小檗碱吴茱萸碱联用对AGS细胞TNF-α和IL-8含量的影响

Effect of Coadministration of Berberine and Evodiamine on TNF-α and IL-8 Levels in AGS Cells

摘要:

目的: 观察小檗碱吴茱萸碱对胃癌细胞株(AGS)细胞增殖及肿瘤坏死因子-α(TNF-α)和白细胞介素(IL-8)含量的影响。方法: 采用MTT(四甲基偶氮唑盐)法测定小檗碱、吴茱萸碱及两药联用对AGS细胞生长的影响;流式细胞技术检测小檗碱、吴茱萸碱及两药联用对AGS细胞细胞周期的影响;ELISA法测定小檗碱、吴茱萸碱及两药联用 对AGS细胞TNF-α和IL-8含量的影响。结果: 小檗碱15 μmol·L^-1和吴茱萸碱45 μmol·L^-1联用时对AGS细胞增殖的抑制作 用弱于吴茱萸碱单用;小檗碱83 μmol·L^-1和吴茱萸碱1.4 μmol·L^-1 联用时对AGS细胞增殖的抑制作用稍优于两药单用,两药联用阻滞细胞周期于G₂/M期的作用较两药单用无显著差异。进一步研究发现,小檗碱83 μmol·L^-1和吴茱萸碱1.4 μmol·L^-1联用增加AGS细胞培养上清肿瘤坏死因子-α(TNF-α)含量的作用优于两药单用。小檗碱具有降低AGS细胞培养上清IL-8含量的趋势,而吴茱萸碱能够显著增强AGS细胞培养上清IL-8的含量(P <0.01),两药联用能够显著降低AGS细胞培养上清中IL-8的含量(P <0.01)。结论: 不同剂量的小檗碱吴茱萸碱联用对AGS细胞增殖的影响不同。小檗碱能够抑制吴茱萸碱诱导的AGS细胞IL-8的表达上调。

Abstract:

Objective: To investigate the effects of coadministration of berberine and evodiamine on cell growth, tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 levels of gastric cancer cells(AGS) cells. Method: The inhibitory effect of coadministration of berberine and evodiamine on AGS cell growth was measured by MTT method. Cell cycle distributions were measured by flow cytometry. TNF-α and IL-8 contents were measured by ELISA method. Result: Coadministration of berberine (15 μmol·L^-1) and evodiamine (45 μmol·L^-1) triggered weaker inhibitory effect on the proliferation of AGS cells than that achieved by evodiamine alone, coadministration of berberine (83 μmol·L^-1) and evodiamine (1.4 μmol·L^-1) obtained slightly better inhibitory effect on the proliferation of AGS cells than that of berberine or evodiamine alone, however, their co-administration did not obtain better cell cycle arrest than berberine or evodiamine alone. Further studies showed that, co-administration of berberine (83 μmol·L^-1) and evodiamine (1.4 μmol·L^-1) induced the increase of TNF-α level in AGS cell culture supernatant which was superior to that triggered by usage of the two drugs alone. Berberine reduced IL-8 contents in the AGS cell culture supernatant but without significance difference, while, evodiamine could significantly enhance the IL-8 contents in AGS cells culture supernatant. Then their coadministration could significantly reduce the IL-8 levels in the AGS cell culture supernatant. Conclusion: Different doses of berberine and evodiamine combination can result in different effect on the proliferation of AGS cells. And berberine could inhibit the increase of IL-8 induced by evodiamine.