• 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

粘着斑激酶抑制剂PF562271对人骨肉瘤的体内外抗肿瘤作用

Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo.

作者信息

Hu Chuanzhen, Chen Xu, Wen Junxiang, Gong Liangzhi, Liu Zhuochao, Wang Jun, Liang Jing, Hu Fangqiong, Zhou Qi, Wei Li, Shen Yuhui, Zhang Weibin

机构信息

Department of Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopedics and Traumatology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Cancer Sci. 2017 Jul;108(7):1347-1356. doi: 10.1111/cas.13256. Epub 2017 Jun 8.

DOI:10.1111/cas.13256
PMID:28406574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5497929/
Abstract

Focal adhesion kinase (FAK) overexpression is related to invasive and metastatic properties in different kinds of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatments, but its effect in human osteosarcoma has not been well studied. In the present study, we analyzed the antitumor efficacy of PF562271, an FAK inhibitor, against osteosarcoma in vitro and in vivo. Phosphorylated FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed proliferation and colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired the tube formation ability of endothelial cells in vitro. Finally, oral treatment with PF562271 in mice dramatically reduced tumor volume, weight, and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma.

摘要

粘着斑激酶（FAK）的过表达与不同类型癌症的侵袭和转移特性相关。通过抑制FAK进行靶向治疗在某些癌症治疗中已取得了有前景的效果，但其在人类骨肉瘤中的作用尚未得到充分研究。在本研究中，我们分析了FAK抑制剂PF562271在体外和体内对骨肉瘤的抗肿瘤疗效。磷酸化FAK（Y397）在原发性人类骨肉瘤肿瘤样本中高表达，且与骨肉瘤预后和肺转移相关。PF562271极大地抑制了人类骨肉瘤细胞系的增殖和集落形成。此外，用PF562271处理骨肉瘤细胞系可诱导细胞凋亡，并下调蛋白激酶B/雷帕霉素哺乳动物靶标通路的活性。PF562271在体外还损害了内皮细胞的管腔形成能力。最后，在小鼠中口服PF562271显著降低了体内骨肉瘤异种移植物的肿瘤体积、重量和血管生成。这些结果表明，FAK抑制剂PF562271可能有效地用于治疗骨肉瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/96a186fbf1dc/CAS-108-1347-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/60f7f1cde0b5/CAS-108-1347-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/9043bc9a7901/CAS-108-1347-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/e15e55b234c9/CAS-108-1347-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/f13da79defed/CAS-108-1347-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/9b84e2401857/CAS-108-1347-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/7aa26a4840a9/CAS-108-1347-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/96a186fbf1dc/CAS-108-1347-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/60f7f1cde0b5/CAS-108-1347-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/9043bc9a7901/CAS-108-1347-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/e15e55b234c9/CAS-108-1347-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/f13da79defed/CAS-108-1347-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/9b84e2401857/CAS-108-1347-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/7aa26a4840a9/CAS-108-1347-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e9b/5497929/96a186fbf1dc/CAS-108-1347-g007.jpg

相似文献

1
Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo.粘着斑激酶抑制剂PF562271对人骨肉瘤的体内外抗肿瘤作用
Cancer Sci. 2017 Jul;108(7):1347-1356. doi: 10.1111/cas.13256. Epub 2017 Jun 8.
2
3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo.3-羟基黄酮通过影响上皮-间质转化（EMT）并经由黏着斑激酶（FAK）-Src至丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK/ERK）和RhoA/肌球蛋白轻链2（MLC2）途径抑制尿激酶型纤溶酶原激活剂（u-PA）/基质金属蛋白酶-2（MMP-2），从而抑制人骨肉瘤U2OS和143B细胞转移，并在体内减少143B肿瘤生长。
Food Chem Toxicol. 2016 Nov;97:177-186. doi: 10.1016/j.fct.2016.09.006. Epub 2016 Sep 4.
3
Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy.焦点黏着激酶自身磷酸化抑制可降低结肠癌细胞的生长，并增强化疗的疗效。
Cancer Biol Ther. 2013 Aug;14(8):761-72. doi: 10.4161/cbt.25185. Epub 2013 Jun 3.
4
Antitumour effects of Yangzheng Xiaoji in human osteosarcoma: the pivotal role of focal adhesion kinase signalling.抑瘤作用的 Yangzheng Xiaoji 人骨肉瘤：黏着斑激酶信号通路的关键作用。
Oncol Rep. 2013 Sep;30(3):1405-13. doi: 10.3892/or.2013.2586. Epub 2013 Jul 3.
5
Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo.针对粘着斑激酶和胰岛素样生长因子-I受体的双酪氨酸激酶抑制剂在体外和体内对食管腺癌均具有抗癌作用。
Clin Cancer Res. 2008 Jul 15;14(14):4631-9. doi: 10.1158/1078-0432.CCR-07-4755.
6
Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271.选择性粘着斑激酶抑制剂PF-562,271的抗肿瘤活性及药理学
Cancer Res. 2008 Mar 15;68(6):1935-44. doi: 10.1158/0008-5472.CAN-07-5155.
7
Inhibition of Src phosphorylation alters metastatic potential of osteosarcoma in vitro but not in vivo.抑制Src磷酸化可改变骨肉瘤在体外的转移潜能，但在体内则不然。
Clin Cancer Res. 2009 May 15;15(10):3416-22. doi: 10.1158/1078-0432.CCR-08-1657.
8
SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway.SLC25A22通过PTEN信号通路促进骨肉瘤细胞的增殖和转移。
Technol Cancer Res Treat. 2018 Jan 1;17:1533033818811143. doi: 10.1177/1533033818811143.
9
Focal adhesion kinase confers pro-migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma.黏着斑激酶赋予迁移促进和抗凋亡特性，是尤文肉瘤潜在的治疗靶点。
Mol Oncol. 2020 Feb;14(2):248-260. doi: 10.1002/1878-0261.12610. Epub 2019 Dec 21.
10
Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program.儿科临床前试验计划用新型黏着斑激酶（FAK）抑制剂 VS-4718 对儿科肿瘤模型进行初步测试。
Pediatr Blood Cancer. 2017 Apr;64(4). doi: 10.1002/pbc.26304. Epub 2016 Oct 27.

引用本文的文献

1
The Role of Pyk2 Kinase in Glioblastoma Progression and Therapeutic Targeting.Pyk2激酶在胶质母细胞瘤进展及治疗靶向中的作用
Cancers (Basel). 2025 Aug 9;17(16):2611. doi: 10.3390/cancers17162611.
2
Transforming Cancer Therapy: Unlocking the Potential of Targeting Vascular and Stromal Cells in the Tumor Microenvironment.变革癌症治疗：挖掘肿瘤微环境中靶向血管和基质细胞的潜力
Cancer Res. 2025 Apr 2. doi: 10.1158/0008-5472.CAN-24-4744.
3
Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies.

本文引用的文献

1
mTOR: An attractive therapeutic target for osteosarcoma?mTOR：骨肉瘤一个有吸引力的治疗靶点？
Oncotarget. 2016 Aug 2;7(31):50805-50813. doi: 10.18632/oncotarget.9305.
2
FAK and paxillin, two potential targets in pancreatic cancer.黏着斑激酶和桩蛋白，胰腺癌的两个潜在靶点。
Oncotarget. 2016 May 24;7(21):31586-601. doi: 10.18632/oncotarget.8040.
3
Expression of pY397 FAK promotes the development of non-small cell lung cancer.磷酸化酪氨酸397位点的粘着斑激酶（pY397 FAK）的表达促进非小细胞肺癌的发展。
通过单细胞RNA测序表征高级别浆液性卵巢癌的肿瘤生物学和免疫微环境：对靶向和个性化免疫治疗策略的见解
Front Immunol. 2025 Jan 17;15:1500153. doi: 10.3389/fimmu.2024.1500153. eCollection 2024.
4
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.利用肿瘤微环境：通过调节上皮-间质转化实现靶向癌症治疗
J Hematol Oncol. 2025 Jan 13;18(1):6. doi: 10.1186/s13045-024-01634-6.
5
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.粘着斑激酶-YAP信号轴驱动肺癌中的药物耐受持久性细胞和残留疾病。
Nat Commun. 2024 May 3;15(1):3741. doi: 10.1038/s41467-024-47423-0.
6
Pyk2/FAK Signaling Is Upregulated in Recurrent Glioblastoma Tumors in a C57BL/6/GL261 Glioma Implantation Model.Pyk2/FAK 信号在 C57BL/6/GL261 胶质瘤植入模型的复发性脑肿瘤中上调。
Int J Mol Sci. 2023 Aug 30;24(17):13467. doi: 10.3390/ijms241713467.
7
FAK inhibitor PF-562271 inhibits the migration and proliferation of high-grade serous ovarian cancer cells through FAK and FAK mediated cell cycle arrest.FAK 抑制剂 PF-562271 通过 FAK 和 FAK 介导的细胞周期阻滞抑制高级别浆液性卵巢癌细胞的迁移和增殖。
Med Oncol. 2023 Jun 29;40(8):215. doi: 10.1007/s12032-023-02092-9.
8
LOX upregulates FAK phosphorylation to promote metastasis in osteosarcoma.赖氨酰氧化酶上调粘着斑激酶磷酸化以促进骨肉瘤转移。
Genes Dis. 2022 Jan 29;10(1):254-266. doi: 10.1016/j.gendis.2021.12.016. eCollection 2023 Jan.
9
The PYK2 inhibitor PF-562271 enhances the effect of temozolomide on tumor growth in a C57Bl/6-Gl261 mouse glioma model.PYK2 抑制剂 PF-562271 增强了替莫唑胺在 C57Bl/6-Gl261 小鼠脑胶质瘤模型中的肿瘤生长抑制作用。
J Neurooncol. 2023 Feb;161(3):593-604. doi: 10.1007/s11060-023-04260-3. Epub 2023 Feb 15.
10
Cancer cells inhibition by cationic carbon dots targeting the cellular nucleus.阳离子碳点靶向细胞核抑制癌细胞。
J Colloid Interface Sci. 2023 May;637:193-206. doi: 10.1016/j.jcis.2023.01.086. Epub 2023 Jan 21.
Oncol Lett. 2016 Feb;11(2):979-983. doi: 10.3892/ol.2015.3992. Epub 2015 Dec 3.
4
Focal adhesion kinase overexpression and its impact on human osteosarcoma.粘着斑激酶过表达及其对人骨肉瘤的影响。
Oncotarget. 2015 Oct 13;6(31):31085-103. doi: 10.18632/oncotarget.5044.
5
mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma.mTORC1维持SSEA-4(+)高级别骨肉瘤的致瘤性。
Sci Rep. 2015 Apr 8;5:9604. doi: 10.1038/srep09604.
6
FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer cells.粘着斑激酶（FAK）激活是胰岛素样生长因子1受体（IGF1R）介导的间充质三阴性乳腺癌细胞上皮-间质转化（EMT）、迁移和侵袭调控所必需的。
Oncotarget. 2015 Mar 10;6(7):4757-72. doi: 10.18632/oncotarget.3023.
7
Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma.互补性基因组学方法凸显了PI3K/mTOR信号通路是骨肉瘤中一种常见的脆弱靶点。
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5564-73. doi: 10.1073/pnas.1419260111. Epub 2014 Dec 15.
8
Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.索拉非尼和依维莫司治疗标准治疗后进展的不可切除高级别骨肉瘤患者：一项非随机 2 期临床试验。
Lancet Oncol. 2015 Jan;16(1):98-107. doi: 10.1016/S1470-2045(14)71136-2. Epub 2014 Dec 11.
9
Translational biology of osteosarcoma.骨肉瘤的转化生物学。
Nat Rev Cancer. 2014 Nov;14(11):722-35. doi: 10.1038/nrc3838. Epub 2014 Oct 16.
10
FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics.使用小分子抑制剂Y15抑制黏着斑激酶（FAK）可降低甲状腺癌细胞系的活力、克隆形成能力和细胞黏附，并与靶向治疗药物产生协同作用。
Oncotarget. 2014 Sep 15;5(17):7945-59. doi: 10.18632/oncotarget.2381.