【摘要】 目的 探究多氧环己烯酮Zeylenone（Zey）逆转肺癌顺铂耐药作用及相关分子机制。方法 使用肺癌A549亲本细胞（A549P）和肺癌A549顺铂耐药细胞（A549cisR），首先用CCK8法检测顺铂或Zey对这两种细胞增殖的影响，然后在顺铂中加入Zey共同作用于A549cisR细胞，利用中位效应法评估联用效果及计算逆转倍数。采用分子对接技术探究Zey与范科尼贫血症（FA）通路相关蛋白的相互作用，最后通过分子动力学模拟和Western blot实验验证Zey对FA通路关键蛋白FANCD2的影响。结果 Zey对A549P和A549cisR细胞增殖均有良好的抑制作用，IC₅₀值相近。Zey显著增加A549cisR细胞对顺铂的敏感性，并可通过抑制FA通路的活性逆转肺癌细胞对顺铂的耐药。结论 Zey可通过影响FA通路FANCD2蛋白逆转肺癌顺铂耐药，该结果可为后续开发Zey为新型耐药逆转剂提供数据支撑。更多还原

【Abstract】 Objective To determine the effect of Zeylenone（Zey） on reversing cisplatin resistance in lung cancer and related molecular mechanism. Methods Lung cancer A549 parent cells（A549P） and lung cancer A549 cisplatin resistant cells（A549cisR） were used. Firstly, CCK8 method was used to detect the effect of cisplatin or Zey on the proliferation of these two cells, and then Zey was added to cisplatin to jointly act on A549cisR cells. The median effect method was used to evaluate the combined effect and calculate the reversal times. Then, the interaction between Zey and the related protein of Fanconi anemia（FA） pathway was determined by molecular docking. Finally, the influence of Zey on the key protein FANCD2 of FA pathway was verified by molecular dynamics simulation and Western blot. Results Zey not only had a good inhibitory effect on A549P, but also a good inhibitory effect on A549cisR, with similar IC₅₀ value. Zey greatly increased the sensitivity of A549cisR to cisplatin and reversed the resistance of lung cancer cells to cisplatin by inhibiting the activity of the FA pathway. Conclusion Zey can reverse cisplatin resistance in lung cancer by affecting FANCD2 protein in FA pathway. Providing data support for the development of Zey as a novel drug resistance reversal agent.更多还原