Cisplatin has been clinically used for treatment of solid tumors such as non–small‐cell lung cancer for decades. However, tumor resistance may be acquired with losing the antitumor activity of cisplatin. As cellular membrane is the first barrier that cisplatin has to overcome before its further action inside the cells, the membrane composition must play a vital role in the cisplatin uptake and excretion, which further influences cisplatin sensitivity. In this work, we applied time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) surface analysis combined with principle component analysis to distinguish the differences of cell membrane composition between non–small‐cell lung cancer cells (A549) and its cisplatin resistant counterpart A549/DDP cells. The decreased phosphatidylcholine content and more abundant cholesterol were observed in the drug resistant cell surfaces, indicating the decreased membrane fluidity of A549/DDP cells. Moreover, we further compared membrane composition of A549 and A549/DDP cells after being treated with different concentrations of cisplatin. A higher composition level of proteins was discovered on all groups of A549/DDP cell membranes. The altered surface chemistry of cellular membranes induced by cisplatin indicates the significance of membrane structures in the drug resistance, which deserves further investigations to this regard.

中文翻译：

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ToF‐SIMS揭示了顺铂诱导的A549细胞膜组成的改变

顺铂已在临床上用于治疗实体瘤，例如非小细胞肺癌已有数十年的历史。然而，在失去顺铂的抗肿瘤活性的情况下可能获得肿瘤抗性。由于细胞膜是顺铂在细胞内进一步发挥作用之前必须克服的第一个障碍，因此膜成分必须在顺铂的摄取和排泄中起至关重要的作用，从而进一步影响顺铂的敏感性。在这项工作中，我们将飞行时间二次离子质谱（ToF-SIMS）表面分析与主成分分析相结合，以区分非小细胞肺癌细胞（A549）与顺铂之间的细胞膜组成差异抗性的对应A549 / DDP细胞。在耐药细胞表面观察到磷脂酰胆碱含量降低，胆固醇含量更高，表明A549 / DDP细胞膜流动性降低。此外，我们进一步比较了用不同浓度的顺铂处理后的A549和A549 / DDP细胞的膜组成。在所有A549 / DDP细胞膜组上发现了更高的蛋白质组成水平。顺铂诱导的细胞膜表面化学性质的改变表明，膜结构在耐药性中具有重要意义，这方面值得进一步研究。在所有A549 / DDP细胞膜组上发现了更高的蛋白质组成水平。顺铂诱导的细胞膜表面化学改变表明，膜结构在耐药性中具有重要意义，这方面值得进一步研究。在所有A549 / DDP细胞膜组上发现了更高的蛋白质组成水平。顺铂诱导的细胞膜表面化学性质的改变表明，膜结构在耐药性中具有重要意义，这方面值得进一步研究。