• 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

达沙替尼通过抑制膀胱癌细胞中的 PI3K/Akt/mTOR 通路诱导细胞凋亡和自噬。

Dasatinib induces apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in bladder cancer cells.

机构信息

Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.

Department of Urology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Investig Clin Urol. 2024 Nov;65(6):593-602. doi: 10.4111/icu.20240250.

DOI:10.4111/icu.20240250
PMID:39505519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11543652/
Abstract

PURPOSE

Bladder cancer is a common genitourinary malignant disease worldwide. Dasatinib is a small molecule inhibitor of Src family kinases. We investigated the anticancer effect and putative molecular mechanisms of dasatinib on T24 and cisplatin-resistant T24R2 human bladder cancer cells.

MATERIALS AND METHODS

Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) and colony formation in dasatinib treated bladder cancer cells. Flow cytometry was used to determined cell cycle arrest and apoptosis. The expression of apoptosis and autophagy related proteins were detected by western blot analysis.

RESULTS

In bladder cancer cells, dasatinib significantly reduced cell proliferation, colony formation, and induced G1-phase arrest. Dasatinib triggered apoptosis along with an increased expression of apoptosis-related genes (caspases, PARP, and cytochrome c). Down-regulation of Bcl-2 and up-regulation of Bad, which are hallmarks of apoptosis, were found to play a dominant role in mediating the effects of dasatinib treatment. We further showed that dasatinib inhibits p-Src, p-PI3K, p-Akt, and p-mTOR in bladder cancer cells. Dasatinib also increased the expression of markers of autophagy flux such as LC3-II and p62.

CONCLUSIONS

These results confirmed that dasatinib is a potent chemotherapeutic drug which induces apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in bladder cancer cells.

摘要

目的

膀胱癌是一种常见的泌尿生殖系统恶性肿瘤。达沙替尼是一种Src 家族激酶小分子抑制剂。我们研究了达沙替尼对 T24 和顺铂耐药 T24R2 人膀胱癌细胞的抗癌作用及其潜在的分子机制。

材料与方法

用细胞计数试剂盒-8（CCK-8）和达沙替尼处理的膀胱癌细胞中的集落形成来测量细胞增殖。流式细胞术用于确定细胞周期停滞和细胞凋亡。通过 Western blot 分析检测凋亡和自噬相关蛋白的表达。

结果

在膀胱癌细胞中，达沙替尼显著降低细胞增殖、集落形成，并诱导 G1 期停滞。达沙替尼触发细胞凋亡，同时增加凋亡相关基因（半胱天冬酶、PARP 和细胞色素 c）的表达。下调 Bcl-2 和上调 Bad，这是凋亡的标志，被发现在介导达沙替尼治疗的作用中起主导作用。我们进一步表明，达沙替尼抑制膀胱癌细胞中的 p-Src、p-PI3K、p-Akt 和 p-mTOR。达沙替尼还增加了自噬通量标志物如 LC3-II 和 p62 的表达。

结论

这些结果证实，达沙替尼是一种有效的化疗药物，通过抑制膀胱癌细胞中的 PI3K/Akt/mTOR 通路诱导细胞凋亡和自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/badb12ccbe06/icu-65-593-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/a231ebda7a81/icu-65-593-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/d12410b07612/icu-65-593-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/5a3864a4d047/icu-65-593-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/abfc796dd66a/icu-65-593-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/abfce3c951f9/icu-65-593-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/ad143ead6569/icu-65-593-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/d54f5096917e/icu-65-593-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/badb12ccbe06/icu-65-593-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/a231ebda7a81/icu-65-593-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/d12410b07612/icu-65-593-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/5a3864a4d047/icu-65-593-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/abfc796dd66a/icu-65-593-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/abfce3c951f9/icu-65-593-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/ad143ead6569/icu-65-593-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/d54f5096917e/icu-65-593-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b6/11543652/badb12ccbe06/icu-65-593-g008.jpg

相似文献

1
Dasatinib induces apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in bladder cancer cells.达沙替尼通过抑制膀胱癌细胞中的 PI3K/Akt/mTOR 通路诱导细胞凋亡和自噬。
Investig Clin Urol. 2024 Nov;65(6):593-602. doi: 10.4111/icu.20240250.
2
Leflunomide Inhibits Proliferation and Induces Apoptosis via Suppressing Autophagy and PI3K/Akt Signaling Pathway in Human Bladder Cancer Cells.来氟米特通过抑制自噬和 PI3K/Akt 信号通路抑制人膀胱癌细胞增殖并诱导其凋亡。
Drug Des Devel Ther. 2020 May 18;14:1897-1908. doi: 10.2147/DDDT.S252626. eCollection 2020.
3
Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway.二甲双胍通过抑制膀胱癌细胞迁移和生长，并通过 PI3K/AKT/mTOR 通路促进细胞凋亡来发挥抗肿瘤作用。
BMC Urol. 2022 May 24;22(1):79. doi: 10.1186/s12894-022-01027-2.
4
Latcripin-7A from Lentinula edodes C induces apoptosis, autophagy, and cell cycle arrest at G1 phase in human gastric cancer cells via inhibiting PI3K/Akt/mTOR signaling.香菇（Lentinula edodes）Latcripin-7A 通过抑制 PI3K/Akt/mTOR 信号通路诱导人胃癌细胞凋亡、自噬和 G1 期细胞周期停滞。
Eur J Pharmacol. 2021 Sep 15;907:174305. doi: 10.1016/j.ejphar.2021.174305. Epub 2021 Jul 2.
5
Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway.红景天苷通过 PI3K/Akt/mTOR 通路诱导人胃癌 AGS 细胞凋亡和保护性自噬。
Biomed Pharmacother. 2020 Feb;122:109726. doi: 10.1016/j.biopha.2019.109726. Epub 2019 Dec 30.
6
Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells.达努塞替布是一种强效的泛极光激酶和ABL激酶抑制剂，可诱导细胞周期停滞和程序性细胞死亡，并在人胃癌AGS和NCI-N78细胞中抑制涉及PI3K/Akt/mTOR介导的信号通路的上皮-间质转化。
Drug Des Devel Ther. 2015 Mar 2;9:1293-318. doi: 10.2147/DDDT.S74964. eCollection 2015.
7
Danusertib Induces Apoptosis, Cell Cycle Arrest, and Autophagy but Inhibits Epithelial to Mesenchymal Transition Involving PI3K/Akt/mTOR Signaling Pathway in Human Ovarian Cancer Cells.达纳替尼诱导人卵巢癌细胞凋亡、细胞周期阻滞和自噬，但通过PI3K/Akt/mTOR信号通路抑制上皮-间质转化
Int J Mol Sci. 2015 Nov 13;16(11):27228-51. doi: 10.3390/ijms161126018.
8
Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells.自噬抑制增强了RAD001对人膀胱癌细胞的细胞毒性。
Drug Des Devel Ther. 2016 Apr 18;10:1501-13. doi: 10.2147/DDDT.S95900. eCollection 2016.
9
Negative regulation of PI3K/AKT/mTOR axis regulates fibroblast proliferation, apoptosis and autophagy play a vital role in triptolide-induced epidural fibrosis reduction.负向调控 PI3K/AKT/mTOR 轴在三萜内酯减轻硬膜外纤维化中的作用，调控成纤维细胞增殖、凋亡和自噬。
Eur J Pharmacol. 2019 Dec 1;864:172724. doi: 10.1016/j.ejphar.2019.172724. Epub 2019 Oct 7.
10
Autophagy limits the cytotoxic effects of the AKT inhibitor AZ7328 in human bladder cancer cells.自噬限制 AKT 抑制剂 AZ7328 对人膀胱癌细胞的细胞毒性作用。
Cancer Biol Ther. 2012 Nov;13(13):1325-38. doi: 10.4161/cbt.21793. Epub 2012 Aug 16.

引用本文的文献

1
Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review).晚期食管鳞状细胞癌的变化格局：全身治疗的突破（综述）
Oncol Rep. 2025 Oct;54(4). doi: 10.3892/or.2025.8953. Epub 2025 Jul 19.
2
Targeting senescence in Amyotrophic Lateral Sclerosis: senolytic treatment improves neuromuscular function and preserves cortical excitability in a TDP-43 mouse model.靶向肌萎缩侧索硬化症中的衰老：衰老细胞溶解疗法改善了TDP-43小鼠模型的神经肌肉功能并保留了皮质兴奋性
Res Sq. 2025 Mar 26:rs.3.rs-6081213. doi: 10.21203/rs.3.rs-6081213/v1.

本文引用的文献

1
Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.非受体酪氨酸激酶：它们在肿瘤进展和耐药中的结构及机制作用
Cancers (Basel). 2024 Aug 2;16(15):2754. doi: 10.3390/cancers16152754.
2
Role of c-Src in Carcinogenesis and Drug Resistance.c-Src在致癌作用和耐药性中的作用。
Cancers (Basel). 2023 Dec 20;16(1):32. doi: 10.3390/cancers16010032.
3
The emerging potential role of p62 in cancer treatment by regulating metabolism.p62 在调节代谢中治疗癌症的新兴潜在作用。
Trends Endocrinol Metab. 2023 Aug;34(8):474-488. doi: 10.1016/j.tem.2023.05.004. Epub 2023 Jun 20.
4
Autophagy and autophagy-related pathways in cancer.自噬和癌症中的自噬相关途径。
Nat Rev Mol Cell Biol. 2023 Aug;24(8):560-575. doi: 10.1038/s41580-023-00585-z. Epub 2023 Mar 2.
5
Dasatinib enhances curcumin-induced cytotoxicity, apoptosis and protective autophagy in human schwannoma cells HEI-193: The role of Akt/mTOR/p70S6K signalling pathway.达沙替尼增强姜黄素诱导的人雪旺氏细胞瘤细胞HEI-193的细胞毒性、凋亡和保护性自噬：Akt/mTOR/p70S6K信号通路的作用
Acta Pharm. 2022 Apr 13;72(3):403-414. doi: 10.2478/acph-2022-0025. Print 2022 Sep 1.
6
The Role of mTOR Signaling as a Therapeutic Target in Cancer.mTOR 信号在癌症治疗中的作用。
Int J Mol Sci. 2021 Feb 9;22(4):1743. doi: 10.3390/ijms22041743.
7
Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far.Src家族激酶作为晚期实体瘤的治疗靶点：我们目前所了解的情况。
Cancers (Basel). 2020 Jun 2;12(6):1448. doi: 10.3390/cancers12061448.
8
Nuclear Functions of the Tyrosine Kinase Src.Src 酪氨酸激酶的核功能
Int J Mol Sci. 2020 Apr 11;21(8):2675. doi: 10.3390/ijms21082675.
9
Autophagy as a molecular target for cancer treatment.自噬作为癌症治疗的分子靶点。
Eur J Pharm Sci. 2019 Jun 15;134:116-137. doi: 10.1016/j.ejps.2019.04.011. Epub 2019 Apr 11.
10
Dasatinib can enhance paclitaxel and gemcitabine inhibitory activity in human pancreatic cancer cells.达沙替尼可增强紫杉醇和吉西他滨对人胰腺癌细胞的抑制活性。
Cancer Biol Ther. 2019;20(6):855-865. doi: 10.1080/15384047.2019.1579956. Epub 2019 Mar 13.