• 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

墨汁中的硫酸化多糖靶向Akt并克服膀胱癌对FGFR抑制剂AZD4547的耐药性。

Sulfated polysaccharide of ink targets Akt and overcomes resistance to the FGFR inhibitor AZD4547 in bladder cancer.

作者信息

Shan Liping, Liu Wei, Zhan Yunhong

机构信息

Department of Urology, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, China.

Emergency Department, First Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Aging (Albany NY). 2019 Sep 23;11(18):7780-7795. doi: 10.18632/aging.102286.

DOI:10.18632/aging.102286
PMID:31545294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6782013/
Abstract

Rapid appearance of resistance to fibroblast growth factor receptor (FGFR) inhibitors hampers targeted regimens in bladder cancer. In the present study, we evaluated whether SIP-SII, a sulphated derivative of the polysaccharide in (spineless cuttlefish) ink used in traditional Chinese medicine, could attenuate resistance to FGFR inhibition in bladder cancer cells. In vitro assays indicated that SIP-SII reduced cell viability and migration, restricted cell cycle progression, and increased apoptosis in parallel with decreased AKT phosphorylation and downregulation of CDK4, MMP2, and Bcl-2 in RT112 and JMSU1 cells. Synergistic effects on cell viability were observed when SIP-SII was combined with the small-molecule FGFR inhibitor AZD4547. Specific Akt targeting by SIP-SII was suggested by the fact that neither Akt knockdown nor the selective PI3K inhibitor BKM120 enhanced the inhibitory effects of SIP-II, while expression of a constitutively active Akt mutant rescued SIP-SII effects. Furthermore, subcutaneous transplantation of RT112 xenografts confirmed the superiority and tolerability of combined SIP-SII and AZD4547 administration over monotherapy regimens. The present study thus provides pre-clinical evidence of the ability of SIP-SII to improve FGFR-targeted therapies for bladder cancer by inhibiting Akt.

摘要

对成纤维细胞生长因子受体（FGFR）抑制剂的耐药性迅速出现，阻碍了膀胱癌的靶向治疗方案。在本研究中，我们评估了中药（乌贼）墨汁中多糖的硫酸化衍生物SIP-SII是否能减弱膀胱癌细胞对FGFR抑制的耐药性。体外试验表明，SIP-SII降低了细胞活力和迁移能力，限制了细胞周期进程，并增加了细胞凋亡，同时RT112和JMSU1细胞中的AKT磷酸化降低，CDK4、MMP2和Bcl-2表达下调。当SIP-SII与小分子FGFR抑制剂AZD4547联合使用时，观察到对细胞活力的协同作用。SIP-SII对Akt的特异性靶向作用体现在以下方面：Akt基因敲低或选择性PI3K抑制剂BKM120均未增强SIP-II的抑制作用，而组成型活性Akt突变体的表达挽救了SIP-SII的作用。此外，RT112异种移植瘤的皮下移植证实了联合使用SIP-SII和AZD4547优于单一治疗方案。因此，本研究提供了临床前证据，证明SIP-SII能够通过抑制Akt来改善膀胱癌的FGFR靶向治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/f85c1be6bf72/aging-11-102286-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/251d4e9c3130/aging-11-102286-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/19b80103885a/aging-11-102286-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/bfbae40abf82/aging-11-102286-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/4c6c570ebf26/aging-11-102286-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/c957d6f75187/aging-11-102286-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/f85c1be6bf72/aging-11-102286-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/251d4e9c3130/aging-11-102286-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/19b80103885a/aging-11-102286-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/bfbae40abf82/aging-11-102286-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/4c6c570ebf26/aging-11-102286-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/c957d6f75187/aging-11-102286-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8063/6782013/f85c1be6bf72/aging-11-102286-g006.jpg

相似文献

1
Sulfated polysaccharide of ink targets Akt and overcomes resistance to the FGFR inhibitor AZD4547 in bladder cancer.墨汁中的硫酸化多糖靶向Akt并克服膀胱癌对FGFR抑制剂AZD4547的耐药性。
Aging (Albany NY). 2019 Sep 23;11(18):7780-7795. doi: 10.18632/aging.102286.
2
Inhibition of EGF-induced migration and invasion by sulfated polysaccharide of Sepiella maindroni ink via the suppression of EGFR/Akt/p38 MAPK/MMP-2 signaling pathway in KB cells.通过抑制 EGFR/Akt/p38 MAPK/MMP-2 信号通路抑制头足类墨囊多糖对 EGF 诱导的 KB 细胞迁移和侵袭的抑制作用。
Biomed Pharmacother. 2017 Nov;95:95-102. doi: 10.1016/j.biopha.2017.08.050. Epub 2017 Aug 19.
3
Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells.曼氏无针乌贼墨多糖通过抑制 EGFR 介导的 p38/MAPK 和 PI3K/Akt/mTOR 信号通路抑制 SKOV-3 细胞的迁移、侵袭和基质金属蛋白酶-2 的表达。
Int J Biol Macromol. 2018 Feb;107(Pt A):349-362. doi: 10.1016/j.ijbiomac.2017.08.178. Epub 2017 Sep 9.
4
A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma.一项功能遗传学筛查确定了磷酸肌醇 3-激酶通路是 FGFR 突变型尿路上皮细胞癌对成纤维细胞生长因子受体抑制剂产生耐药的决定因素。
Eur Urol. 2017 Jun;71(6):858-862. doi: 10.1016/j.eururo.2017.01.021. Epub 2017 Jan 17.
5
Inhibition activity of sulfated polysaccharide of Sepiella maindroni ink on matrix metalloproteinase (MMP)-2.曼氏无针乌贼墨汁硫酸化多糖对基质金属蛋白酶（MMP）-2的抑制活性。
Biomed Pharmacother. 2008 Jun;62(5):297-302. doi: 10.1016/j.biopha.2008.01.018. Epub 2008 Feb 20.
6
Mechanisms of Efficacy of the FGFR1-3 Inhibitor AZD4547 in Pediatric Solid Tumor Models.FGFR1-3 抑制剂 AZD4547 在儿科实体瘤模型中的疗效机制。
Invest New Drugs. 2020 Dec;38(6):1677-1686. doi: 10.1007/s10637-020-00933-2. Epub 2020 May 20.
7
Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.曼氏无针乌贼墨多糖的抗转移和抗血管生成活性。
Carbohydr Polym. 2013 Jan 2;91(1):403-9. doi: 10.1016/j.carbpol.2012.08.050. Epub 2012 Aug 22.
8
AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer.AZD4547 靶向 FGFR/Akt/SOX2 轴以克服头颈部癌症对紫杉醇的耐药性。
Cell Oncol (Dordr). 2022 Feb;45(1):41-56. doi: 10.1007/s13402-021-00645-6. Epub 2021 Nov 27.
9
Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance.肿瘤细胞对新型成纤维细胞生长因子受体酪氨酸激酶抑制剂的反应及 FGFR3 中的一个守门突变作为获得性耐药机制的鉴定。
Oncogene. 2013 Jun 20;32(25):3059-70. doi: 10.1038/onc.2012.319. Epub 2012 Aug 6.
10
Study on the preparation and biological activities of low molecular weight squid ink polysaccharide from Sepiella maindroni.曼氏无针乌贼低分子量墨汁多糖的制备及生物活性研究。
Int J Biol Macromol. 2023 May 15;237:124040. doi: 10.1016/j.ijbiomac.2023.124040. Epub 2023 Mar 16.

引用本文的文献

1
Retraction of: Apigenin inhibits growth and migration of fibroblasts by suppressing FAK signaling.撤回：芹菜素通过抑制FAK信号通路抑制成纤维细胞的生长和迁移。
Aging (Albany NY). 2025 Mar 31;17(3):883-884. doi: 10.18632/aging.206230.
2
Retraction of: miR-627-3p inhibits osteosarcoma cell proliferation and metastasis by targeting PTN.撤回：miR-627-3p通过靶向PTN抑制骨肉瘤细胞增殖和转移
Aging (Albany NY). 2024 Oct 15;16(19):12953-12954. doi: 10.18632/aging.206128.
3
The Role of Long Non-Coding RNF144A-AS1 in Cancer Progression.

本文引用的文献

1
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018：GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
2
Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547.转录组学和转座子诱变鉴定 FGFR 抑制剂 AZD4547 耐药的多种机制。
Cancer Res. 2018 Oct 1;78(19):5668-5679. doi: 10.1158/0008-5472.CAN-18-0757. Epub 2018 Aug 16.
3
Acquired JHDM1D-BRAF Fusion Confers Resistance to FGFR Inhibition in -Amplified Gastric Cancer.
长链非编码RNA RNF144A-AS1在癌症进展中的作用。
Cell Biochem Biophys. 2024 Sep;82(3):2007-2017. doi: 10.1007/s12013-024-01411-9. Epub 2024 Jul 16.
4
New Directions and Challenges in Targeted Therapies of Advanced Bladder Cancer: The Role of FGFR Inhibitors.晚期膀胱癌靶向治疗的新方向与挑战：FGFR抑制剂的作用
Cancers (Basel). 2022 Mar 10;14(6):1416. doi: 10.3390/cancers14061416.
5
ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A.ALK2 通过靶向 DEPDC1A 作为膀胱癌发展的肿瘤促进剂。
Cell Death Dis. 2021 Jul 1;12(7):661. doi: 10.1038/s41419-021-03947-7.
6
Integrated metabolomics and transcriptomics reveal the anti-aging effect of melanin from ink (MSMI) on D-galactose-induced aging mice.整合代谢组学和转录组学揭示了墨汁黑色素（MSMI）对 D-半乳糖诱导衰老小鼠的抗衰老作用。
Aging (Albany NY). 2021 Apr 21;13(8):11889-11906. doi: 10.18632/aging.202890.
JHDM1D-BRAF 融合获得性耐药 FGFR 抑制在 FGFR 扩增的胃癌中。
Mol Cancer Ther. 2018 Oct;17(10):2217-2225. doi: 10.1158/1535-7163.MCT-17-1022. Epub 2018 Jul 25.
4
Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.肌层浸润性膀胱癌的综合分子特征分析
Cell. 2017 Oct 19;171(3):540-556.e25. doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.
5
Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells.曼氏无针乌贼墨多糖通过抑制 EGFR 介导的 p38/MAPK 和 PI3K/Akt/mTOR 信号通路抑制 SKOV-3 细胞的迁移、侵袭和基质金属蛋白酶-2 的表达。
Int J Biol Macromol. 2018 Feb;107(Pt A):349-362. doi: 10.1016/j.ijbiomac.2017.08.178. Epub 2017 Sep 9.
6
Inhibition of EGF-induced migration and invasion by sulfated polysaccharide of Sepiella maindroni ink via the suppression of EGFR/Akt/p38 MAPK/MMP-2 signaling pathway in KB cells.通过抑制 EGFR/Akt/p38 MAPK/MMP-2 信号通路抑制头足类墨囊多糖对 EGF 诱导的 KB 细胞迁移和侵袭的抑制作用。
Biomed Pharmacother. 2017 Nov;95:95-102. doi: 10.1016/j.biopha.2017.08.050. Epub 2017 Aug 19.
7
Comprehensive Molecular Characterization of Urothelial Bladder Carcinoma: A Step Closer to Clinical Translation?尿路上皮膀胱癌的综合分子特征：离临床转化更近一步了吗？
Eur Urol. 2017 Dec;72(6):960-961. doi: 10.1016/j.eururo.2017.06.022. Epub 2017 Jul 5.
8
Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in Patients with Muscle-Invasive Bladder Cancer.依维莫司联合三联疗法治疗肌层浸润性膀胱癌的I期临床试验
Bladder Cancer. 2017 Apr 27;3(2):105-112. doi: 10.3233/BLC-160090.
9
A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma.一项功能遗传学筛查确定了磷酸肌醇 3-激酶通路是 FGFR 突变型尿路上皮细胞癌对成纤维细胞生长因子受体抑制剂产生耐药的决定因素。
Eur Urol. 2017 Jun;71(6):858-862. doi: 10.1016/j.eururo.2017.01.021. Epub 2017 Jan 17.
10
Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study.在晚期实体瘤的日本患者中，成纤维细胞生长因子受体抑制剂 AZD4547 的安全性、耐受性和药代动力学：一项 I 期研究。
Invest New Drugs. 2017 Aug;35(4):451-462. doi: 10.1007/s10637-016-0416-x. Epub 2017 Jan 10.