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艾伏尼布通过降低癌细胞干性增强卵巢癌对顺铂的敏感性。

Ivosidenib enhances cisplatin sensitivity in ovarian cancer by reducing cancer cell stemness.

作者信息

Chen Mengqing, Huang Lin, Zhao Simei, Zhu Mengna, Sun Si, Li Wenhan, Cai Jing, Peng Minggang, Wen Yiping, Wang Zehua

机构信息

Authors contributed equally.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

出版信息

Cancer Drug Resist. 2025 Apr 24;8:20. doi: 10.20517/cdr.2025.51. eCollection 2025.

DOI:10.20517/cdr.2025.51
PMID:40342735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12059478/
Abstract

: Cancer stem cells (CSCs) are pivotal in mediating platinum resistance in ovarian cancer. This study aimed to screen compounds sensitizing CSCs to cisplatin by using a small molecule inhibitor library. : A library of 105 common drugs was screened in ovarian CSC model SK-3rd and ovarian cancer platinum-resistant cell model SKDDP to identify those that could enhance sensitivity to cisplatin by MTT assay. The antitumor effect was assessed in ovarian cancer cells using the MTT assay, colony formation assay, and apoptosis assay. The impact on cancer cell stemness was evaluated using qPCR and Sphere-forming assays. Finally, the effect of the combination regimen was evaluated in patient-derived organoids (PDOs) under different treatments by the CellTiter-Glo Luminescence Assay. : The results of the initial screening on SK-3rd identified five candidate compounds. Rescreening on SKDDP showed that Ivosidenib was the most effective in sensitizing cisplatin. MTT, colony formation, and apoptosis assays demonstrated that Ivosidenib enhanced the sensitivity to cisplatin, inhibited proliferation, and induced apoptosis in ovarian cancer cells, including SK-3rd and SKDDP. Furthermore, Ivosidenib lowered stemness marker expression and countered CSC enrichment caused by platinum-based chemotherapy in ovarian cancer cells. Finally, the synergistic effect of this combination was also confirmed in three ovarian cancer PDOs. : Ivosidenib may increase cisplatin sensitivity in ovarian cancer cells by decreasing their stemness, providing a potential therapeutic method for ovarian cancer patients.

摘要

癌症干细胞（CSCs）在介导卵巢癌对铂类药物的耐药性中起关键作用。本研究旨在通过使用小分子抑制剂文库筛选使CSCs对顺铂敏感的化合物。

在卵巢癌CSC模型SK - 3rd和卵巢癌铂耐药细胞模型SKDDP中筛选了105种常用药物的文库，通过MTT法确定那些能增强对顺铂敏感性的药物。使用MTT法、集落形成试验和凋亡试验评估对卵巢癌细胞的抗肿瘤作用。使用qPCR和球形成试验评估对癌细胞干性的影响。最后，通过CellTiter - Glo发光试验在不同治疗下的患者来源类器官（PDOs）中评估联合治疗方案的效果。

对SK - 3rd的初步筛选结果确定了5种候选化合物。在SKDDP上的重新筛选表明，艾伏尼布在使顺铂敏感方面最有效。MTT、集落形成和凋亡试验表明，艾伏尼布增强了对顺铂的敏感性，抑制了卵巢癌细胞（包括SK - 3rd和SKDDP）的增殖并诱导了凋亡。此外，艾伏尼布降低了干性标志物的表达，并对抗了铂类化疗导致的卵巢癌细胞中CSC的富集。最后，在三种卵巢癌PDOs中也证实了这种联合的协同作用。

艾伏尼布可能通过降低卵巢癌细胞的干性来增加其对顺铂的敏感性，为卵巢癌患者提供了一种潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/1bdd70513244/cdr-8-20.fig.6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/60137520c7e7/cdr-8-20.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/6657e0dfd955/cdr-8-20.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/fa69a706cbe9/cdr-8-20.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/d891fe66753a/cdr-8-20.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/410ce45d3111/cdr-8-20.fig.5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/1bdd70513244/cdr-8-20.fig.6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/60137520c7e7/cdr-8-20.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/6657e0dfd955/cdr-8-20.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/fa69a706cbe9/cdr-8-20.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/d891fe66753a/cdr-8-20.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/410ce45d3111/cdr-8-20.fig.5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/12059478/1bdd70513244/cdr-8-20.fig.6.jpg

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