• 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

idelalisib可诱导结肠癌细胞发生依赖于PUMA的凋亡。

Idelalisib induces PUMA-dependent apoptosis in colon cancer cells.

作者信息

Yang Shida, Zhu Zhiyong, Zhang Xiaobing, Zhang Ning, Yao Zhicheng

机构信息

Department of Laboratory Medicine, The People's Hospital of Liaoning Province, Shenyang, China.

Department of Orthopedics, The People's Hospital of Liaoning Province, Shenyang, China.

出版信息

Oncotarget. 2017 Jan 24;8(4):6102-6113. doi: 10.18632/oncotarget.14043.

DOI:10.18632/oncotarget.14043
PMID:28008149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5351616/
Abstract

Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications.

摘要

idelalisib是一种PI3K抑制剂，特异性靶向p110δ，已被批准用于治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤和滤泡性淋巴瘤。然而，idelalisib在结肠癌细胞中的作用机制尚不完全清楚。我们研究了idelalisib如何抑制结肠癌细胞生长并增强其他化疗药物的效果。在本研究中，我们发现idelalisib处理通过AKT抑制和糖原合酶激酶3β（GSK3β）激活后的p65途径，在结肠癌细胞中诱导PUMA，而与p53状态无关。PUMA是idelalisib诱导结肠癌细胞凋亡所必需的。Idelalisib还与5-氟尿嘧啶或瑞戈非尼协同作用，通过PUMA在结肠癌细胞中诱导显著凋亡。此外，PUMA缺陷抑制了idelalisib在异种移植模型中的凋亡和抗肿瘤作用。这些结果证明了PUMA在介导idelalisib对结肠癌细胞的抗癌作用中的关键作用，并表明PUMA诱导可作为idelalisib敏感性的指标，对其临床应用也具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/bd441c9622e8/oncotarget-08-6102-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/639c9d740a53/oncotarget-08-6102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/90685e9792d1/oncotarget-08-6102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/ed312538d380/oncotarget-08-6102-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/c400147e9d31/oncotarget-08-6102-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/23a538f3a5c8/oncotarget-08-6102-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/bd441c9622e8/oncotarget-08-6102-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/639c9d740a53/oncotarget-08-6102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/90685e9792d1/oncotarget-08-6102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/ed312538d380/oncotarget-08-6102-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/c400147e9d31/oncotarget-08-6102-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/23a538f3a5c8/oncotarget-08-6102-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc13/5351616/bd441c9622e8/oncotarget-08-6102-g006.jpg

相似文献

1
Idelalisib induces PUMA-dependent apoptosis in colon cancer cells.idelalisib可诱导结肠癌细胞发生依赖于PUMA的凋亡。
Oncotarget. 2017 Jan 24;8(4):6102-6113. doi: 10.18632/oncotarget.14043.
2
Crizotinib induces PUMA-dependent apoptosis in colon cancer cells.克唑替尼诱导结肠癌细胞中 PUMA 依赖性凋亡。
Mol Cancer Ther. 2013 May;12(5):777-86. doi: 10.1158/1535-7163.MCT-12-1146. Epub 2013 Feb 20.
3
Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis.瑞戈非尼通过PUMA介导的细胞凋亡抑制结直肠癌肿瘤生长。
Clin Cancer Res. 2014 Jul 1;20(13):3472-84. doi: 10.1158/1078-0432.CCR-13-2944. Epub 2014 Apr 24.
4
Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.卡博替尼通过 AKT/GSK-3β/NF-κB 信号通路诱导结肠癌细胞中 PUMA 依赖性凋亡。
Cancer Gene Ther. 2020 May;27(5):368-377. doi: 10.1038/s41417-019-0098-6. Epub 2019 Jun 11.
5
Pazopanib, a novel multi-kinase inhibitor, shows potent antitumor activity in colon cancer through PUMA-mediated apoptosis.帕唑帕尼，一种新型多激酶抑制剂，通过PUMA介导的凋亡在结肠癌中显示出强大的抗肿瘤活性。
Oncotarget. 2017 Jan 10;8(2):3289-3303. doi: 10.18632/oncotarget.13753.
6
Inhibiting oncogenic signaling by sorafenib activates PUMA via GSK3β and NF-κB to suppress tumor cell growth.索拉非尼通过 GSK3β 和 NF-κB 抑制致癌信号来激活 PUMA，从而抑制肿瘤细胞生长。
Oncogene. 2012 Nov 15;31(46):4848-58. doi: 10.1038/onc.2011.644. Epub 2012 Jan 30.
7
MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism.MEK5/ERK5信号通路抑制通过p53依赖机制增加结肠癌细胞对5-氟尿嘧啶的敏感性。
Oncotarget. 2016 Jun 7;7(23):34322-40. doi: 10.18632/oncotarget.9107.
8
PUMA mediates the combinational therapy of 5-FU and NVP-BEZ235 in colon cancer.PUMA介导5-氟尿嘧啶和NVP-BEZ235联合治疗结肠癌。
Oncotarget. 2015 Jun 10;6(16):14385-98. doi: 10.18632/oncotarget.3775.
9
Aurora kinase inhibition induces PUMA via NF-κB to kill colon cancer cells.极光激酶抑制通过 NF-κB 诱导 PUMA 杀死结肠癌细胞。
Mol Cancer Ther. 2014 May;13(5):1298-308. doi: 10.1158/1535-7163.MCT-13-0846. Epub 2014 Feb 21.
10
Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis.伊帕替膦酸盐，一种新型 Akt 抑制剂，直接诱导转录因子 FoxO3a，NF-κB 直接调控 PUMA 依赖性凋亡。
Cell Death Dis. 2018 Sep 5;9(9):911. doi: 10.1038/s41419-018-0943-9.

引用本文的文献

1
PI3Kδ as a Novel Therapeutic Target for Aggressive Prostate Cancer.PI3Kδ作为侵袭性前列腺癌的新型治疗靶点。
Cancers (Basel). 2025 May 9;17(10):1610. doi: 10.3390/cancers17101610.
2
Senolytic Flavonoids Enhance Type-I and Type-II Cell Death in Human Radioresistant Colon Cancer Cells through AMPK/MAPK Pathway.衰老细胞裂解性黄酮类化合物通过AMPK/MAPK途径增强人放射性抗性结肠癌细胞中的I型和II型细胞死亡。
Cancers (Basel). 2023 May 8;15(9):2660. doi: 10.3390/cancers15092660.
3
Downregulation of microRNA‑494 inhibits cell proliferation in lung squamous cell carcinoma via the induction of PUMA‑α‑mediated apoptosis.

本文引用的文献

1
FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation.FBW7突变通过阻断Mcl-1降解介导结直肠癌对靶向治疗的耐药性。
Oncogene. 2017 Feb 9;36(6):787-796. doi: 10.1038/onc.2016.247. Epub 2016 Jul 11.
2
BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells.BRAFV600E 依赖性的 Mcl-1 稳定导致结肠癌细胞对依维莫司耐药。
Oncotarget. 2016 Jul 26;7(30):47699-47710. doi: 10.18632/oncotarget.10277.
3
Outcomes of patients with chronic lymphocytic leukemia treated with first-line idelalisib plus rituximab after cessation of treatment for toxicity.
微小RNA-494的下调通过诱导PUMA-α介导的凋亡抑制肺鳞状细胞癌的细胞增殖。
Exp Ther Med. 2023 Apr 11;25(6):242. doi: 10.3892/etm.2023.11941. eCollection 2023 Jun.
4
Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.2011年至2019年美国食品药品监督管理局批准的手性小分子抗肿瘤靶向药物的最新研究进展
Front Oncol. 2021 Dec 17;11:785855. doi: 10.3389/fonc.2021.785855. eCollection 2021.
5
The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy.p53功能障碍在结直肠癌中的作用及其对治疗的意义。
Cancers (Basel). 2021 May 11;13(10):2296. doi: 10.3390/cancers13102296.
6
Emerging treatment options for patients with p53-pathway-deficient CLL.针对p53通路缺陷型慢性淋巴细胞白血病患者的新兴治疗选择。
Ther Adv Hematol. 2019 Dec 5;10:2040620719891356. doi: 10.1177/2040620719891356. eCollection 2019.
7
Mutant p53 drives cancer chemotherapy resistance due to loss of function on activating transcription of PUMA.突变型 p53 通过丧失 PUMA 的激活转录功能导致癌症化疗耐药。
Cell Cycle. 2019 Dec;18(24):3442-3455. doi: 10.1080/15384101.2019.1688951. Epub 2019 Nov 14.
8
Targeting Akt by SC66 triggers GSK-3β mediated apoptosis in colon cancer therapy.在结肠癌治疗中，通过SC66靶向Akt可触发GSK-3β介导的细胞凋亡。
Cancer Cell Int. 2019 May 9;19:124. doi: 10.1186/s12935-019-0837-7. eCollection 2019.
9
Trastuzumab induces PUMA-dependent apoptosis and inhibits tumor growth in gastric cancer.曲妥珠单抗诱导胃癌中PUMA依赖的细胞凋亡并抑制肿瘤生长。
FEBS Open Bio. 2018 Nov 19;8(12):1911-1919. doi: 10.1002/2211-5463.12522. eCollection 2018 Dec.
10
Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma.依鲁替尼通过 AKT/FoxO3a 促进肝癌细胞中的 Bim 依赖性细胞凋亡。
Cell Death Dis. 2018 Sep 17;9(10):935. doi: 10.1038/s41419-018-0960-8.
因毒性而停止治疗后接受一线idelalisib联合利妥昔单抗治疗的慢性淋巴细胞白血病患者的结局
Cancer. 2016 Aug 15;122(16):2505-11. doi: 10.1002/cncr.30069. Epub 2016 May 16.
4
Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL.idelalisib与entospletinib的2期研究：肺炎限制了复发难治性慢性淋巴细胞白血病和非霍奇金淋巴瘤的联合治疗。
Blood. 2016 May 19;127(20):2411-5. doi: 10.1182/blood-2015-12-683516. Epub 2016 Mar 11.
5
Idelalisib for treatment of B-cell malignancies.idelalisib用于治疗B细胞恶性肿瘤。
Am J Health Syst Pharm. 2016 Apr 15;73(8):547-55. doi: 10.2146/ajhp150281. Epub 2016 Mar 1.
6
The PI3Kδ inhibitor idelalisib suppresses liver and lung cellular respiration.PI3Kδ抑制剂idelalisib可抑制肝脏和肺细胞的呼吸作用。
Int J Physiol Pathophysiol Pharmacol. 2015 Dec 13;7(3):115-25. eCollection 2015.
7
Breakthrough therapies in B-cell non-Hodgkin lymphoma.B 细胞非霍奇金淋巴瘤的突破性疗法。
Ann Oncol. 2016 May;27(5):778-87. doi: 10.1093/annonc/mdw029. Epub 2016 Jan 22.
8
Cancer statistics, 2016.癌症统计数据，2016 年。
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.
9
A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia.一项关于idelalisib联合利妥昔单抗用于初治老年慢性淋巴细胞白血病患者的2期研究。
Blood. 2015 Dec 17;126(25):2686-94. doi: 10.1182/blood-2015-03-630947. Epub 2015 Oct 15.
10
Vertical suppression of the EGFR pathway prevents onset of resistance in colorectal cancers.表皮生长因子受体（EGFR）通路的垂直抑制可预防结直肠癌耐药性的发生。
Nat Commun. 2015 Sep 22;6:8305. doi: 10.1038/ncomms9305.