IRE1α inhibitor reduces cisplatin resistance in ovarian cancer by modulating IRE1α/XBP1 pathway.

IF 4.9 2区医学 Q2 CELL BIOLOGY Cellular Oncology Pub Date : 2024-11-20 DOI:10.1007/s13402-024-01010-z

Shiyi Lv, Lin Zhang, Min Wu, Shuangshuang Zhu, Yixue Wang, Layang Liu, Yunxuan Li, Ting Zhang, Yujie Wu, Huang Chen, Mingyao Liu, Zhengfang Yi

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Abstract

Ovarian cancer, a leading cause of gynecological cancer deaths globally, poses significant treatment challenges. Cisplatin (CDDP) is the first treatment choice for ovarian cancer and it is initially effective. However, 80% of ovarian cancer patients eventually relapse and develop resistance, resulting in chemotherapy failure. Therefore, finding new treatment combinations to overcome ovarian cancer resistance can provide a new tactic to improve the ovarian cancer patients' survival rate. We first identified activation of the Unfolded Protein Response (UPR) in CDDP-resistant ovarian cancer cells, implicating the IRE1α/XBP1 pathway in promoting resistance. Our findings demonstrate that inhibiting IRE1α signaling can re-sensitizes resistant cells to CDDP in vivo and in vitro, suggesting that IRE1α inhibitor used in conjunction with CDDP presumably could merge as a novel therapeutic strategy. Here, our research highlights the critical role of IRE1α signaling in mediating CDDP resistance, and paves the way for improved treatment options through combinatorial therapy.

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IRE1α抑制剂通过调节IRE1α/XBP1通路降低卵巢癌的顺铂耐药性

卵巢癌是全球妇科癌症死亡的主要原因，给治疗带来了巨大挑战。顺铂（CDDP）是卵巢癌的首选治疗药物，而且在初期疗效显著。然而，80% 的卵巢癌患者最终会复发并产生抗药性，导致化疗失败。因此，寻找克服卵巢癌耐药性的新的治疗组合为提高卵巢癌患者的生存率提供了新的策略。我们首次发现 CDDP 耐药卵巢癌细胞中存在未折叠蛋白反应（UPR）的激活，这与促进耐药性的 IRE1α/XBP1 通路有关。我们的研究结果表明，抑制IRE1α信号传导可使体内和体外对CDDP耐药的细胞重新敏感，这表明IRE1α抑制剂与CDDP结合使用可能会成为一种新的治疗策略。在此，我们的研究强调了IRE1α信号传导在介导CDDP耐药性中的关键作用，并为通过组合疗法改善治疗方案铺平了道路。

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.