苏州大学应征 研究小组近日取得一项新成果。经过不懈努力，他们的最新研究揭示了非小细胞肺癌细胞维持细胞质无膜细胞器的相分离以保护自己免受顺铂治疗。这一研究成果发表在2025年4月17日出版的国际学术期刊《中国药理学报》上。

该研究组揭示了非小细胞肺癌顺铂耐药的新分子基础，表明顺铂通过改变细胞质无膜细胞器杀死癌细胞。具体而言，顺铂治疗导致加工体（PBs）的解体和应激颗粒（SG）样颗粒的组装，这些颗粒与NSCLC细胞中的典型SGs不同，但不是顺铂耐药的NSCLC细胞。

此外，PBs和非典型SG样颗粒的改变与顺铂诱导的癌细胞死亡有关。重要的是，该研究团队发现用环己亚胺和FDA-批准的吡啶破坏PBs和标准SGs有助于顺铂杀死顺铂耐药的NSCLC细胞。综上所述，他们的发现揭示了无膜细胞器调控在顺铂耐药中的作用，并为克服非小细胞肺癌顺铂耐药提供了有效的解决方案。

据了解，顺铂是首个以抗癌为主题的铂类化合物，包括非小细胞肺癌（NSCLC）。然而，顺铂的临床疗效受到顺铂耐药的强烈限制。因此，阐明顺铂耐药的机制将有助于开发改善癌细胞对顺铂敏感性的治疗策略。有趣的是，通过与相分离相关的生物分子凝聚形成的无膜细胞器最近与癌症有关。

附：英文原文

Title: NSCLC cells sustain phase separation of cytoplasmic membrane-less organelles to protect themselves against cisplatin treatment

Author: Li, Ning-ning, Rao, Ling-ling, Su, Dan, Liu, Bin-hao, Ma, Guo-qiang, Wang, Hong-feng, Zhang, Zeng-li, Ying, Zheng

Issue&Volume: 2025-04-17

Abstract: Cisplatin is the first platinum compound used for anticancer therapy, including non-small cell lung cancer (NSCLC). However, the clinical efficacy of cisplatin is strongly limited by cisplatin resistance. Hence, illuminating the mechanism of cisplatin resistance will aid in the development of therapeutic strategies that improve the sensitivity of cancer cells to cisplatin. Interestingly, membrane-less organelles, which are formed through biomolecular condensation in association with phase separation, have been recently linked with cancers. Here, we reveal a new molecular basis of cisplatin resistance in NSCLC, showing that cisplatin kills cancer cells by the alteration of cytoplasmic membrane-less organelles. Specifically, cisplatin treatment results in the disassembly of processing bodies (PBs) and the assembly of stress granule (SG)-like granules which are different from canonical SGs in NSCLC cells, but not cisplatin-resistant NSCLC cells. Moreover, alterations of PBs and noncanonical SG-like granules are associated with cisplatin-induced cancer cell death. Importantly, we found that disrupting PBs and canonical SGs with cycloheximide and FDA-approved pyrvinium helps cisplatin to kill cisplatin-resistant NSCLC cells. Taken together, our findings provide insight into the role of membrane-less organelle regulation in cisplatin resistance and offer an effective solution for overcoming cisplatin resistance in NSCLC.

DOI: 10.1038/s41401-025-01551-5

Source: https://www.nature.com/articles/s41401-025-01551-5