• 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

二甲双胍通过抑制FAK/Akt信号通路抑制宫颈癌迁移。

Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.

作者信息

Hakimee Henna, Hutamekalin Pilaiwanwadee, Tanasawet Supita, Chonpathompikunlert Pennapa, Tipmanee Varomyalin, Sukketsiri Wanida

机构信息

Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Department of Physiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla,Thailand.

出版信息

Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3539-3545. doi: 10.31557/APJCP.2019.20.12.3539.

DOI:10.31557/APJCP.2019.20.12.3539
PMID:31870092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7173373/
Abstract

BACKGROUND

Metformin, an antidiabetic drug, has been previously reported to have anti-cancer activities. However, its role in the control of cancer cell migration remains elusive.

METHODS

To examine the possible effect of metformin on migration of cervical cancer cells. The related mechanisms were further determined by immunocytochemistry and Western's blotting assay.

RESULTS

The results showed that metformin treatment substantially inhibited the migration ability of cervical cancer cells. Consistently, the filopodia and lamellipodia formation were depleted after exposure to metformin. The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.

CONCLUSION

Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein. We propose that metformin could be a novel potential candidate as an antimetastatic cancer drug in the cervical cancer management.

摘要

背景

二甲双胍是一种抗糖尿病药物,此前有报道称其具有抗癌活性。然而,其在控制癌细胞迁移方面的作用仍不清楚。

方法

为了研究二甲双胍对宫颈癌细胞迁移的可能影响。通过免疫细胞化学和蛋白质印迹分析进一步确定相关机制。

结果

结果表明,二甲双胍处理显著抑制了宫颈癌细胞的迁移能力。同样,暴露于二甲双胍后,丝状伪足和片状伪足的形成减少。二甲双胍处理后,通过诸如粘着斑激酶(FAK)、ATP依赖性酪氨酸激酶(Akt)、Rac1和RhoA等调节蛋白介导的迁移受到抑制。

结论

二甲双胍通过抑制丝状伪足和片状伪足的形成,抑制FAK、Akt及其下游的Rac1和RhoA蛋白,从而在宫颈癌细胞中发挥抗迁移作用。我们认为,二甲双胍可能是宫颈癌治疗中一种新型的潜在抗转移癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/2847f5c68088/APJCP-20-3539-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/23399cbebbe5/APJCP-20-3539-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/2f501d7e4c56/APJCP-20-3539-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/1e837d3646de/APJCP-20-3539-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/25c03b2658e6/APJCP-20-3539-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/2847f5c68088/APJCP-20-3539-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/23399cbebbe5/APJCP-20-3539-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/2f501d7e4c56/APJCP-20-3539-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/1e837d3646de/APJCP-20-3539-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/25c03b2658e6/APJCP-20-3539-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5965/7173373/2847f5c68088/APJCP-20-3539-g005.jpg

相似文献

1
Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.二甲双胍通过抑制FAK/Akt信号通路抑制宫颈癌迁移。
Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3539-3545. doi: 10.31557/APJCP.2019.20.12.3539.
2
Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.二甲双胍通过激活 AMPK/p53 轴和抑制 PI3K/AKT 信号通路诱导人宫颈癌细胞凋亡和抑制迁移。
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11725. Epub 2020 Nov 25.
3
Cisplatin at sub-toxic levels mediates integrin switch in lung cancer cells.低毒顺铂介导肺癌细胞整合素转换。
Anticancer Res. 2014 Dec;34(12):7111-7.
4
Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1, with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting Focal Adhesion Kinase/Paxillin Signaling.用新型二吡啶基酮缩氨基硫脲靶向转移抑制因子N- myc下游调控基因-1:通过抑制粘着斑激酶/桩蛋白信号传导抑制肿瘤细胞迁移和细胞-胶原蛋白粘附
Mol Pharmacol. 2016 May;89(5):521-40. doi: 10.1124/mol.115.103044. Epub 2016 Feb 19.
5
14-3-3beta-Rac1-p21 activated kinase signaling regulates Akt1-mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly.14-3-3β-Rac1-p21激活激酶信号传导调节Akt1介导的细胞骨架组织、板状伪足形成和纤连蛋白基质组装。
J Cell Physiol. 2009 Feb;218(2):394-404. doi: 10.1002/jcp.21612.
6
MeHg affects the activation of FAK, Src, Rac1 and Cdc42, critical proteins for cell movement in PDGF-stimulated SH-SY5Y neuroblastoma cells.甲基汞影响 PDGF 刺激的 SH-SY5Y 神经母细胞瘤细胞中细胞运动的关键蛋白 FAK、Src、Rac1 和 Cdc42 的激活。
Toxicology. 2018 Feb 1;394:35-44. doi: 10.1016/j.tox.2017.11.019. Epub 2017 Nov 29.
7
Dieckol from Ecklonia cava suppresses the migration and invasion of HT1080 cells by inhibiting the focal adhesion kinase pathway downstream of Rac1-ROS signaling.裙带菜酚从裙带菜中抑制 HT1080 细胞的迁移和侵袭通过抑制 Rac1-ROS 信号下游的粘着斑激酶途径。
Mol Cells. 2012 Feb;33(2):141-9. doi: 10.1007/s10059-012-2192-6.
8
Batatasin III Inhibits Migration of Human Lung Cancer Cells by Suppressing Epithelial to Mesenchymal Transition and FAK-AKT Signals.甘薯酮III通过抑制上皮-间质转化和FAK-AKT信号通路抑制人肺癌细胞迁移。
Anticancer Res. 2017 Nov;37(11):6281-6289. doi: 10.21873/anticanres.12079.
9
DEF6, a novel PH-DH-like domain protein, is an upstream activator of the Rho GTPases Rac1, Cdc42, and RhoA.DEF6是一种新型的类PH-DH结构域蛋白,是Rho GTP酶Rac1、Cdc42和RhoA的上游激活剂。
Exp Cell Res. 2004 Apr 1;294(2):335-44. doi: 10.1016/j.yexcr.2003.12.004.
10
Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1.抑制 6-磷酸葡萄糖酸脱氢酶通过非 AMPK 依赖途径抑制 RhoA 和 Rac1 增强宫颈癌的化疗疗效。
Clin Transl Oncol. 2019 Apr;21(4):404-411. doi: 10.1007/s12094-018-1937-x. Epub 2018 Sep 4.

引用本文的文献

1
Metformin and its Nanoformulations in Cancer Prevention and Therapy.二甲双胍及其纳米制剂在癌症预防与治疗中的应用
Curr Pharm Des. 2025 Apr 8. doi: 10.2174/0113816128367242250214052019.
2
Autophagy modulation effect on homotypic transfer of intracellular components via tunneling nanotubes in mesenchymal stem cells.自噬对间充质干细胞中通过隧道纳米管进行的细胞内成分同源转移的调节作用。
Stem Cell Res Ther. 2024 Jul 2;15(1):189. doi: 10.1186/s13287-024-03813-1.
3
Changes in the expression of cancer- and metastasis-related genes and proteins after metformin treatment under different metabolic conditions in endometrial cancer cells.

本文引用的文献

1
Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.二甲双胍与奈非那韦联合应用对人宫颈癌细胞生长及裸鼠移植瘤的协同抑制作用
Sci Rep. 2017 Mar 2;7:43373. doi: 10.1038/srep43373.
2
Repurposing old drugs to chemoprevention: the case of metformin.将旧药用于化学预防:二甲双胍的案例。
Semin Oncol. 2016 Feb;43(1):123-133. doi: 10.1053/j.seminoncol.2015.09.009. Epub 2015 Sep 8.
3
The expanding role of metformin in cancer: an update on antitumor mechanisms and clinical development.
在不同代谢条件下,二甲双胍处理子宫内膜癌细胞后癌症和转移相关基因及蛋白表达的变化
Heliyon. 2023 May 25;9(6):e16678. doi: 10.1016/j.heliyon.2023.e16678. eCollection 2023 Jun.
4
MiR-4521 plays a tumor repressive role in growth and metastasis of hepatocarcinoma cells by suppressing phosphorylation of FAK/AKT pathway via targeting FAM129A.miR-4521 通过靶向 FAM129A 抑制 FAK/AKT 通路的磷酸化,在肝癌细胞的生长和转移中发挥肿瘤抑制作用。
J Adv Res. 2021 May 12;36:147-161. doi: 10.1016/j.jare.2021.05.003. eCollection 2022 Feb.
5
Proteomic Analysis Reveals That Metformin Suppresses PSMD2, STIP1, and CAP1 for Preventing Gastric Cancer AGS Cell Proliferation and Migration.蛋白质组学分析表明二甲双胍通过抑制PSMD2、STIP1和CAP1来预防胃癌AGS细胞的增殖和迁移。
ACS Omega. 2021 May 26;6(22):14208-14219. doi: 10.1021/acsomega.1c00894. eCollection 2021 Jun 8.
6
Molecular and Cellular Mechanisms of Metformin in Cervical Cancer.二甲双胍在宫颈癌中的分子与细胞机制
Cancers (Basel). 2021 May 22;13(11):2545. doi: 10.3390/cancers13112545.
7
Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers.线粒体活性氧在恶性肿瘤中的病理和药理作用:涉及化学化合物、天然产物和光敏剂的治疗方法。
Molecules. 2020 Nov 11;25(22):5252. doi: 10.3390/molecules25225252.
二甲双胍在癌症中的作用不断扩大:抗肿瘤机制和临床开发的最新进展。
Target Oncol. 2016 Aug;11(4):447-67. doi: 10.1007/s11523-016-0423-z.
4
Association between Metformin Use and Mortality after Cervical Cancer in Older Women with Diabetes.老年糖尿病女性宫颈癌患者使用二甲双胍与死亡率之间的关联
Cancer Epidemiol Biomarkers Prev. 2016 Mar;25(3):507-12. doi: 10.1158/1055-9965.EPI-15-1008. Epub 2015 Dec 31.
5
Inhibition of the GTPase Rac1 mediates the antimigratory effects of metformin in prostate cancer cells.抑制 GTPase Rac1 介导二甲双胍对前列腺癌细胞的抗迁移作用。
Mol Cancer Ther. 2015 Feb;14(2):586-96. doi: 10.1158/1535-7163.MCT-14-0102. Epub 2014 Dec 19.
6
Understanding the roles of FAK in cancer: inhibitors, genetic models, and new insights.了解 FAK 在癌症中的作用:抑制剂、遗传模型和新见解。
J Histochem Cytochem. 2015 Feb;63(2):114-28. doi: 10.1369/0022155414561498. Epub 2014 Nov 7.
7
Overexpression of RhoA promotes the proliferation and migration of cervical cancer cells.RhoA的过表达促进宫颈癌细胞的增殖和迁移。
Biosci Biotechnol Biochem. 2014;78(11):1895-901. doi: 10.1080/09168451.2014.943650. Epub 2014 Aug 7.
8
Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.二甲双胍和苯乙双胍在细胞转化过程中消耗三羧酸循环和糖酵解中间产物,以及肿瘤干细胞中的 NTP。
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10574-9. doi: 10.1073/pnas.1409844111. Epub 2014 Jul 7.
9
The overexpression of scaffolding protein NEDD9 promotes migration and invasion in cervical cancer via tyrosine phosphorylated FAK and SRC.支架蛋白 NEDD9 的过表达通过酪氨酸磷酸化 FAK 和 SRC 促进宫颈癌的迁移和侵袭。
PLoS One. 2013 Sep 18;8(9):e74594. doi: 10.1371/journal.pone.0074594. eCollection 2013.
10
Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner.二甲双胍通过 AMPK/p53 依赖性途径阻断黑色素瘤的侵袭和转移发展。
Mol Cancer Ther. 2013 Aug;12(8):1605-15. doi: 10.1158/1535-7163.MCT-12-1226-T. Epub 2013 Jun 5.