研究动态
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通过增强 NAD(P) 代谢组来保护化疗期间的生育能力。

Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome.

发表日期:2024 Aug 21
作者: Wing-Hong Jonathan Ho, Maria B Marinova, Dave R Listijono, Michael J Bertoldo, Dulama Richani, Lynn-Jee Kim, Amelia Brown, Angelique H Riepsamen, Safaa Cabot, Emily R Frost, Sonia Bustamante, Ling Zhong, Kaisa Selesniemi, Derek Wong, Romanthi Madawala, Maria Marchante, Dale M Goss, Catherine Li, Toshiyuki Araki, David J Livingston, Nigel Turner, David A Sinclair, Kirsty A Walters, Hayden A Homer, Robert B Gilchrist, Lindsay E Wu
来源: EMBO Molecular Medicine

摘要:

化疗引起的卵巢衰竭和不孕是育龄或更年轻女性癌症患者的一个重要问题,迫切需要非侵入性的药理学方法来维持卵巢功能。鉴于还原型烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 作为药物解毒的重要辅助因子的作用,我们试图测试增强 NAD(P) 代谢组是否可以保护卵巢功能。我们通过卵母细胞产量、卵泡健康和功能性育种试验来衡量,补充 NAD 代谢组的药理学或转基因策略可改善化疗引起的雌性不孕症。重要的是,用 NAD 前体烟酰胺单核苷酸 (NMN) 治疗三阴性乳腺癌小鼠模型可减少肿瘤生长,并且不会损害化疗药物在体内或不同癌细胞系中的疗效。总体而言,这些发现提出了 NAD 前体可能成为维持癌症患者卵巢功能的非侵入性策略的可能性,并在癌症治疗中具有潜在益处。© 2024。作者。
Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.© 2024. The Author(s).