• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

三维培养乳腺癌细胞增强了非酰化 ghrelin 和 AZP-531 的抗肿瘤作用。

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531.

机构信息

Department of Medicine, Weill Cornell Medicine, New York, United States.

Centre for Cancer Research, Hudson Institute for Medical Research, Clayton, Australia.

出版信息

Elife. 2020 Jul 15;9:e56913. doi: 10.7554/eLife.56913.

DOI:10.7554/eLife.56913
PMID:32667883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7363447/
Abstract

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531. We report potent anti-tumor effects of unacylated ghrelin, dependent on cells being cultured in 3D in a biologically-relevant extracellular matrix. The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of Gαi and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

摘要

乳腺癌是女性最常见的癌症类型，尽管在治疗方面取得了重要进展，但仍是癌症相关死亡的第二大主要原因。尽管已经对生长激素释放和食欲的刺激物——胃饥饿素进行了广泛的研究，但对于其未酰化形式的影响知之甚少，尤其是在癌症方面。本研究旨在描述未酰化胃饥饿素对乳腺癌细胞的作用，确定其作用机制，并探索未酰化胃饥饿素或类似物 AZP-531 的治疗潜力。我们报告了未酰化胃饥饿素的强大抗肿瘤作用，这取决于细胞在生物相关的细胞外基质中以 3D 方式培养。未酰化胃饥饿素介导的生长抑制的机制涉及 Gαi 的激活和 MAPK 信号的抑制。AZP-531 还抑制乳腺癌细胞的生长，并在异种移植中抑制其生长，可能是安全有效治疗乳腺癌的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/b6e0de8edda9/elife-56913-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/ac532c0ea4ce/elife-56913-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/7e9f4ae49fec/elife-56913-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/9cc4b93836d8/elife-56913-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/0c230d98ffb8/elife-56913-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/b39fbe325b95/elife-56913-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/e2c3c3495da1/elife-56913-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/34521e02a8ed/elife-56913-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/edaf4b7ea90f/elife-56913-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/448096d7f14e/elife-56913-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/0f2f24d21adb/elife-56913-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/eb7f79e62ffd/elife-56913-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/b6e0de8edda9/elife-56913-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/ac532c0ea4ce/elife-56913-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/7e9f4ae49fec/elife-56913-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/9cc4b93836d8/elife-56913-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/0c230d98ffb8/elife-56913-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/b39fbe325b95/elife-56913-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/e2c3c3495da1/elife-56913-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/34521e02a8ed/elife-56913-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/edaf4b7ea90f/elife-56913-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/448096d7f14e/elife-56913-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/0f2f24d21adb/elife-56913-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/eb7f79e62ffd/elife-56913-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c560/7363447/b6e0de8edda9/elife-56913-resp-fig1.jpg

相似文献

1
Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531.三维培养乳腺癌细胞增强了非酰化 ghrelin 和 AZP-531 的抗肿瘤作用。
Elife. 2020 Jul 15;9:e56913. doi: 10.7554/eLife.56913.
2
Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore.未酰化胃饥饿素类似物独立于通透性转换孔预防心肌再灌注损伤。
Basic Res Cardiol. 2017 Jan;112(1):4. doi: 10.1007/s00395-016-0595-9. Epub 2016 Dec 19.
3
AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.AZP-531，一种未酰化的胃饥饿素类似物，改善普拉德-威利综合征患者与食物相关的行为：一项随机安慰剂对照试验。
PLoS One. 2018 Jan 10;13(1):e0190849. doi: 10.1371/journal.pone.0190849. eCollection 2018.
4
Acylated and unacylated ghrelin inhibit doxorubicin-induced apoptosis in skeletal muscle.酰化和去酰化胃饥饿素可抑制阿霉素诱导的骨骼肌细胞凋亡。
Acta Physiol (Oxf). 2014 May;211(1):201-13. doi: 10.1111/apha.12263. Epub 2014 Apr 2.
5
Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway.胃饥饿素及其未酰化异构体通过抗凋亡途径刺激肾上腺皮质肿瘤细胞的生长。
Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E302-9. doi: 10.1152/ajpendo.00377.2006. Epub 2007 Apr 3.
6
Acylated and unacylated ghrelin inhibit apoptosis in myoblasts cocultured with colon carcinoma cells.酰化和未酰化的生长素抑制与结肠癌细胞共培养的成肌细胞凋亡。
Oncol Rep. 2018 Mar;39(3):1387-1395. doi: 10.3892/or.2018.6213. Epub 2018 Jan 12.
7
Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway.沙利霉素具有抗肿瘤活性，并通过一条不依赖凋亡的途径抑制乳腺癌干细胞样细胞。
Biochem Biophys Res Commun. 2015 Oct 30;466(4):696-703. doi: 10.1016/j.bbrc.2015.09.108. Epub 2015 Sep 25.
8
Acylated and unacylated ghrelin confer neuroprotection to mesencephalic neurons.酰基化和未酰基化的 ghrelin 对中脑神经元具有神经保护作用。
Neuroscience. 2017 Dec 4;365:137-145. doi: 10.1016/j.neuroscience.2017.09.045. Epub 2017 Oct 4.
9
Marine lipopeptide Iturin A inhibits Akt mediated GSK3β and FoxO3a signaling and triggers apoptosis in breast cancer.海洋脂肽伊枯草菌素A抑制Akt介导的GSK3β和FoxO3a信号传导并引发乳腺癌细胞凋亡。
Sci Rep. 2015 May 14;5:10316. doi: 10.1038/srep10316.
10
Sialylation transmogrifies human breast and pancreatic cancer cells into 3D multicellular tumor spheroids using cyclic RGD-peptide induced self-assembly.唾液酸化利用环状RGD肽诱导的自组装将人乳腺癌和胰腺癌细胞转变为三维多细胞肿瘤球体。
Oncotarget. 2016 Oct 4;7(40):66119-66134. doi: 10.18632/oncotarget.11868.

引用本文的文献

1
Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.胃饥饿素诱导的神经元神经肽Y促进低体重指数肺癌患者的脑转移。
Nat Commun. 2025 Jul 1;16(1):5608. doi: 10.1038/s41467-025-60730-4.
2
The Orphan G Protein-Coupled Receptor GPR52 is a Novel Regulator of Breast Cancer Multicellular Organization.孤儿G蛋白偶联受体GPR52是乳腺癌多细胞组织的新型调节因子。
bioRxiv. 2024 Jul 23:2024.07.22.604482. doi: 10.1101/2024.07.22.604482.
3
Ghrelin and Cancer: Examining the Roles of the Ghrelin Axis in Tumor Growth and Progression.

本文引用的文献

1
AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.AZP-531，一种未酰化的胃饥饿素类似物，改善普拉德-威利综合征患者与食物相关的行为：一项随机安慰剂对照试验。
PLoS One. 2018 Jan 10;13(1):e0190849. doi: 10.1371/journal.pone.0190849. eCollection 2018.
2
Therapeutic potential of ghrelin and des-acyl ghrelin against chemotherapy-induced cardiotoxicity.胃饥饿素和去酰基胃饥饿素对化疗诱导的心脏毒性的治疗潜力。
Endocr J. 2017;64(Suppl.):S35-S39. doi: 10.1507/endocrj.64.S35.
3
Ghrelin and Breast Cancer: Emerging Roles in Obesity, Estrogen Regulation, and Cancer.
胃饥饿素与癌症：探讨胃饥饿素轴在肿瘤生长和进展中的作用。
Biomolecules. 2022 Mar 22;12(4):483. doi: 10.3390/biom12040483.
4
Cancer as a homeostatic challenge: the role of the hypothalamus.癌症作为一种体内平衡的挑战：下丘脑的作用。
Trends Neurosci. 2021 Nov;44(11):903-914. doi: 10.1016/j.tins.2021.08.008. Epub 2021 Sep 21.
5
Metabolic pathways in obesity-related breast cancer.肥胖相关乳腺癌中的代谢途径。
Nat Rev Endocrinol. 2021 Jun;17(6):350-363. doi: 10.1038/s41574-021-00487-0. Epub 2021 Apr 29.
6
Roles of Aminoacyl-tRNA Synthetases in Cancer.氨酰-tRNA合成酶在癌症中的作用。
Front Cell Dev Biol. 2020 Nov 27;8:599765. doi: 10.3389/fcell.2020.599765. eCollection 2020.
胃饥饿素与乳腺癌：在肥胖、雌激素调节及癌症中的新作用
Front Oncol. 2017 Jan 9;6:265. doi: 10.3389/fonc.2016.00265. eCollection 2016.
4
Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells.去酰基胃饥饿素抑制巨噬细胞刺激乳腺脂肪基质细胞中芳香化酶表达的能力。
J Steroid Biochem Mol Biol. 2017 Jun;170:49-53. doi: 10.1016/j.jsbmb.2016.07.005. Epub 2016 Jul 14.
5
3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.人表皮生长因子受体2阳性乳腺癌细胞的3D培养促进AKT向MAPK的转换及治疗反应丧失。
BMC Cancer. 2016 Jun 1;16:345. doi: 10.1186/s12885-016-2377-z.
6
Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes.新型酰化人生长激素类似物 AZP-531 在健康人群、超重/肥胖人群和 2 型糖尿病患者中的安全性、耐受性、药代动力学和药效学研究。
Diabetes Obes Metab. 2016 Sep;18(9):868-74. doi: 10.1111/dom.12675. Epub 2016 May 26.
7
Treating cancer with selective CDK4/6 inhibitors.用选择性 CDK4/6 抑制剂治疗癌症。
Nat Rev Clin Oncol. 2016 Jul;13(7):417-30. doi: 10.1038/nrclinonc.2016.26. Epub 2016 Mar 31.
8
Optimal management of hormone receptor positive metastatic breast cancer in 2016.2016年激素受体阳性转移性乳腺癌的优化管理
Ther Adv Med Oncol. 2015 Nov;7(6):304-20. doi: 10.1177/1758834015608993.
9
Integrin-specific hydrogels as adaptable tumor organoids for malignant B and T cells.整合素特异性水凝胶作为恶性B细胞和T细胞的适应性肿瘤类器官
Biomaterials. 2015 Dec;73:110-9. doi: 10.1016/j.biomaterials.2015.09.007. Epub 2015 Sep 11.
10
Activation of KRAS promotes the mesenchymal features of basal-type breast cancer.KRAS的激活促进了基底型乳腺癌的间充质特征。
Exp Mol Med. 2015 Jan 30;47(1):e137. doi: 10.1038/emm.2014.99.