Apatinib inhibits synovial sarcoma progression and angiogenesis via VEGFR2-mediated AKT/FOXO3A and ERK1/2/FOXM1 signaling pathways.

IF 10.4 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2026-06-03 DOI:10.1038/s41420-026-03188-7

Ruijie Liu, Fengzhen Zhang, Kai Shi, Wenhao Wang, Xuewen Li, Shaobo Lu, Bowen Chen, Dongjin Wu, Changliang Peng

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引用次数: 0

Abstract

Synovial sarcoma (SS) is a highly aggressive soft-tissue malignancy with limited therapeutic options for advanced disease. Here, we report that apatinib, a selective VEGFR2 tyrosine kinase inhibitor, exerts potent antitumor and anti-angiogenic activity in SS. In SS cell lines, apatinib reduced cell viability, induced G1 phase arrest, and triggered both apoptosis and autophagy. Apatinib further suppressed the metastatic phenotype by inhibiting cell migration, invasion, and EMT, while simultaneously reducing VEGF expression and impairing endothelial tube formation. Mechanistically, apatinib suppressed the VEGFR2/AKT/FOXO3A and ERK1/2/FOXM1 axes in tumor cells, thereby restraining proliferation and angiogenic signaling, and directly impaired endothelial function via the VEGFR2/AKT/eNOS/NO pathway in HUVECs. In vivo, apatinib markedly suppressed xenograft tumor growth and modulated the corresponding signaling pathways. Collectively, our findings identify apatinib as a promising therapeutic agent that disrupts interconnected survival and angiogenic networks in SS.

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阿帕替尼通过vegfr2介导的AKT/FOXO3A和ERK1/2/FOXM1信号通路抑制滑膜肉瘤的进展和血管生成。

滑膜肉瘤（SS）是一种高度侵袭性的软组织恶性肿瘤，晚期疾病的治疗选择有限。在这里，我们报道了apatinib，一种选择性VEGFR2酪氨酸激酶抑制剂，在SS细胞系中具有有效的抗肿瘤和抗血管生成活性。在SS细胞系中，apatinib降低细胞活力，诱导G1期阻滞，并引发细胞凋亡和自噬。阿帕替尼通过抑制细胞迁移、侵袭和EMT进一步抑制转移表型，同时降低VEGF表达并损害内皮管形成。在机制上，阿帕替尼抑制肿瘤细胞中的VEGFR2/AKT/FOXO3A和ERK1/2/FOXM1轴，从而抑制增殖和血管生成信号，并通过VEGFR2/AKT/eNOS/NO通路直接损害huvec的内皮功能。在体内，阿帕替尼显著抑制异种移植物肿瘤生长并调节相应的信号通路。总的来说，我们的研究结果确定阿帕替尼是一种很有前途的治疗药物，可以破坏SS中相互关联的生存和血管生成网络。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.