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成纤维细胞生长因子受体家族抑制剂 AZD4547 在卵巢癌细胞中发挥抗肿瘤作用。

The FGFR Family Inhibitor AZD4547 Exerts an Antitumor Effect in Ovarian Cancer Cells.

机构信息

Department of Gynecology and Obstetrics, School of Medicine, Keimyung University, Daegu 42601, Korea.

Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Korea.

出版信息

Int J Mol Sci. 2021 Oct 6;22(19):10817. doi: 10.3390/ijms221910817.

Abstract

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.

摘要

成纤维细胞生长因子(FGF)信号的失调与肿瘤发生、肿瘤进展、血管生成和化疗耐药有关。小分子 AZD4547 是一种有效的 FGF 受体抑制剂。本研究旨在探讨 AZD4547 在卵巢癌细胞中的抗肿瘤作用及作用机制。AZD4547 显著抑制卵巢癌细胞的增殖并诱导其凋亡,还能在非毒性条件下抑制卵巢癌细胞的迁移和侵袭,减弱球体的形成和卵巢癌细胞的自我更新能力,并发挥抗血管生成作用。它还能抑制小鼠体内的肿瘤生长。综上所述,本研究表明 AZD4547 对卵巢癌细胞具有抗肿瘤作用,提示其可能成为卵巢癌治疗的一种有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68d3/8509426/1a7d248f3685/ijms-22-10817-g001.jpg

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