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目的 研究以大黄素为母体结构 ,人工半合成的 4种蒽醌衍生物抑制 KB和 KBv2 0 0细胞增殖的作用机制。方法 采用 MTT比色法测定细胞毒作用 ;采用流式细胞仪检测分别用 DCFH- DA和 Di OC6 荧光探针标记的细胞内活性氧 (ROS)和线粒体跨膜电位 (ΔΨm)。结果 4种蒽醌衍生物均能不同程度地抑制 KB和 KBv2 0 0细胞的增殖 ,表现为较强的体外抗肿瘤作用 :1,8-二 (二甲氨乙氨基 ) - 3-甲基 - 6 -甲氧基蒽醌 (H- 19)对 KB和 KBv2 0 0细胞 IC50 分别为 1.37和 1.4 2μmol/ L ;1-吡啶乙氨基 - 3-甲基 - 6 ,8-二甲氧基蒽醌 (H- 2 1)的 IC50 分别是 13.0和17.9μm ol/ L;1-吡咯烷乙氨基 - 3-甲基 - 6 ,8-二甲氧基蒽醌 (H- 2 5 )的 IC50 分别是 8.5和 11.7μmol/ L;1-羟丁氨基 -3-甲基 - 6 ,8-二甲氧基蒽醌 (H - 2 8)的 IC50 分别是 7.6和 8.6μmol/ L ,且各药对敏感株 KB和相应的多药耐药(MDR)细胞 KBv2 0 0的 IC50 相近 (P>0 .0 5 )。用 4种药物分别处理两种细胞 12、2 4、4 8h,12 h即能引起 ROS的明显增加 ,2 4 h达到最大 ,与 4 8h引起的 ROS增加差异不显著 ;各药均引起两种细胞ΔΨm时间依赖性的降低 ,4 8h时 ΔΨm降低达到最大。结论 4种大黄素蒽醌衍生物可能通过诱导细胞内 ROS的增加 ,使得 ΔΨm降低 ,从?
Objective To study the mechanism of the inhibition of the proliferation of KB and KBv200 cells by using emodin as the parent structure and artificial semisynthetic four hydrazine derivatives. Methods Cytotoxicity was determined by MTT colorimetric assay; intracellular reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were measured by flow cytometry using DCFH-DA and Di OC6 fluorescent probes, respectively. RESULTS: The four hydrazine derivatives all inhibited the proliferation of KB and KBv200 cells to varying degrees, showing a strong antitumor effect in vitro: 1,8-bis(dimethylaminoethylamino)-3-methyl- The IC50 of 6-methoxystilbene (H-19) on KB and KBv200 cells were 1.37 and 1.4 2 μmol/L, respectively; 1-pyridylethylamino-3-methyl-6,8-dimethoxypyrene The IC50 of (H-21) is 13.0 and 17.9 μmol/L, respectively; the IC50 of 1-pyrrolidineethylamino-3-methyl-6,8-dimethoxypyrene (H-25) is The IC50s of 8.5 and 11.7 μmol/L; 1-hydroxybutylamino-3-methyl-6,8-dimethoxypyrene (H-28) were 7.6 and 8.6 μmol/L, respectively, and were sensitive to each drug. The IC50 of KBv200 was similar between strain KB and corresponding multidrug resistance (MDR) cells (P>0.05). The two drugs were treated with four drugs for 12, 24 and 48 hours respectively, which caused a significant increase in ROS at 12 h, reached a maximum at 24 h, and showed no significant difference from the increase in ROS caused by 48 h; The cell ΔΨm decreased in a time-dependent manner, and the ΔΨm decreased to the maximum at 48 hours. Conclusion The four emodin derivatives may induce the increase of intracellular ROS and decrease ΔΨm.