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Synergistic effect and its possible mechanisms of lidamycin in combination with TRAIL in NSCLC
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 10
- DOI:
- No doi available
- Key Word:
- 力达霉素;肿瘤坏死因子相关的凋亡诱导配体;细胞凋亡;死亡受体 5
Abstract： 研究力达霉素(LDM)与肿瘤坏死因子相关的凋亡诱导配体(TRAIL)联合作用对非小细胞肺癌细胞株H460细胞的增效作用及其作用机制.MTT法观察两药联合对H460细胞增殖的抑制作用.Annexin V-FITC/PI双染、流式细胞术和Hoechst 33342荧光染色检测两药联合对细胞凋亡的影响.Western blotting检测凋亡通路中PARP、Caspase-3和Caspase-8分子的变化以及LDM对TRAIL受体DR4、DR5表达的影响.MTT结果显示,LDM与TRAIL的IC50值分别为4.603×10-10mol·L-1和915.3 ng·mL-1,在TRAIL(50及100 ng·mL-1)作用下LDM的IC50值分别为3.064×10-11和1.611×10-11 mol·L-1.两药相互作用指数CDI<1.荧光显微镜下观察及流式细胞术检测两药联合细胞凋亡作用增强.联合用药组中Caspase-3和Caspase-8的激活作用明显增强.LDM能够增强TRAIL受体DR5的表达,不仅具有剂量依赖性,且作用时间越长表达量越高.研究结果提示,LDM对人非小细胞肺癌细胞株H460细胞具有生长抑制作用,可能通过诱导DR5表达上调而促进TRAIL诱导的肿瘤细胞凋亡,抑制细胞增殖,从而增加细胞对TRAIL的敏感性.
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