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铜死亡抑制卵巢癌的肿瘤进展并增强顺铂毒性。

Cuproptosis inhibits tumor progression and enhances cisplatin toxicity in ovarian cancer.

作者信息

Zou Qiaojian, Chen Yili, Liu Duo, Du Qiqiao, Zhang Chunyu, Mai Qiuwen, Wang Xiaojun, Lin Xiaoying, Chen Qianrun, Wei Mengxun, Chi Chudan, Yao Shuzhong, Liu Junxiu

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Obstetrics and Gynecology, Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China.

出版信息

FASEB J. 2025 Mar 31;39(6):e70484. doi: 10.1096/fj.202500047R.

Abstract

Cuproptosis is a novel form of regulated cell death triggered by copper ion and copper ionophore. While cuproptosis has been actively explored as a potential target for cancer therapy, its role in ovarian cancer (OC) still remains unclear. In this study, we demonstrate that cuproptosis inhibits OC cell proliferation, migration, and invasion through FDX1 regulation and suppresses tumor growth in a mouse model. We also confirm that cuproptosis enhances OC sensitivity to cisplatin treatment both in vivo and in vitro. Moreover, our findings reveal that cuproptosis affects cholesterol biosynthesis in OC cells, with cholesterol playing a crucial role in its cytotoxic effect. Taken together, our results elucidate the effect of cuproptosis in OC and suggest it as a promising therapeutic strategy.

摘要

铜死亡是由铜离子和铜离子载体触发的一种新型程序性细胞死亡形式。虽然铜死亡作为癌症治疗的潜在靶点已被积极探索,但其在卵巢癌(OC)中的作用仍不清楚。在本研究中,我们证明铜死亡通过FDX1调控抑制OC细胞增殖、迁移和侵袭,并在小鼠模型中抑制肿瘤生长。我们还证实,铜死亡在体内和体外均增强OC对顺铂治疗的敏感性。此外,我们的研究结果表明,铜死亡影响OC细胞中的胆固醇生物合成,胆固醇在其细胞毒性作用中起关键作用。综上所述,我们的结果阐明了铜死亡在OC中的作用,并表明它可能是一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e3/11929041/76f7227e456b/FSB2-39-e70484-g001.jpg

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