• 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

新型外泌体介导Survivin-T34A 突变体递送增强胰腺腺癌对吉西他滨的敏感性。

Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant.

机构信息

Division of Biochemistry & Microbiology, Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Loma Linda University, Loma Linda, CA, USA.

出版信息

J Extracell Vesicles. 2014 Feb 17;3. doi: 10.3402/jev.v3.23244. eCollection 2014.

DOI:10.3402/jev.v3.23244
PMID:24624263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3929070/
Abstract

BACKGROUND

Current therapeutic options for advanced pancreatic cancer have been largely disappointing with modest results at best, and though adjuvant therapy remains controversial, most remain in agreement that Gemcitabine should stand as part of any combination study. The inhibitor of apoptosis (IAP) protein Survivin is a key factor in maintaining apoptosis resistance, and its dominant-negative mutant (Survivin-T34A) has been shown to block Survivin, inducing caspase activation and apoptosis.

METHODS

In this study, exosomes, collected from a melanoma cell line built to harbor a tetracycline-regulated Survivin-T34A, were plated on the pancreatic adenocarcinoma (MIA PaCa-2) cell line. Evaluation of the presence of Survivin-T34A in these exosomes followed by their ability to induce Gemcitabine-potentiative cell killing was the objective of this work.

RESULTS

Here we show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cell do contain Survivin-T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to Gemcitabine alone on a variety of pancreatic cancer cell lines.

CONCLUSION

This exosomes/Survivin-T34A study shows that a new delivery method for anticancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas.

摘要

背景

目前晚期胰腺癌的治疗选择收效甚微，令人失望，尽管辅助治疗仍存在争议，但大多数人仍认为吉西他滨应作为任何联合研究的一部分。凋亡抑制蛋白（IAP）蛋白 Survivin 是维持凋亡抵抗的关键因素，其显性负突变体（Survivin-T34A）已被证明可以阻断 Survivin，诱导半胱天冬酶激活和细胞凋亡。

方法

在这项研究中，从构建了四环素调控 Survivin-T34A 的黑色素瘤细胞系中收集的外泌体被铺在胰腺腺癌细胞系（MIA PaCa-2）上。评估这些外泌体中 Survivin-T34A 的存在，以及它们诱导吉西他滨增效细胞杀伤的能力是这项工作的目的。

结果

在这里，我们展示了从工程化黑色素瘤细胞中在没有四环素（tet-off）的情况下收集的外泌体确实含有 Survivin-T34A，并且当单独使用或与吉西他滨联合使用时，与单独使用吉西他滨相比，在各种胰腺癌细胞系中诱导了明显增加的凋亡细胞死亡。

结论

这项外泌体/Survivin-T34A 研究表明，在癌症微环境中，一种新的抗癌蛋白传递方法可能有助于靶向胰腺癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/2b3e61825b6f/JEV-3-23244-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/b03d5de4aa2c/JEV-3-23244-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/312ad1e1f3a1/JEV-3-23244-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/58ccc6d2cde6/JEV-3-23244-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/f29fd2d71590/JEV-3-23244-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/2b3e61825b6f/JEV-3-23244-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/b03d5de4aa2c/JEV-3-23244-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/312ad1e1f3a1/JEV-3-23244-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/58ccc6d2cde6/JEV-3-23244-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/f29fd2d71590/JEV-3-23244-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00da/3929070/2b3e61825b6f/JEV-3-23244-g005.jpg

相似文献

1
Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant.新型外泌体介导Survivin-T34A 突变体递送增强胰腺腺癌对吉西他滨的敏感性。
J Extracell Vesicles. 2014 Feb 17;3. doi: 10.3402/jev.v3.23244. eCollection 2014.
2
Cloning, expression, and purification of the recombinant pro-apoptotic dominant-negative survivin T34A-C84A protein in Escherichia coli.重组促凋亡显性负性生存素T34A - C84A蛋白在大肠杆菌中的克隆、表达及纯化
Protein Expr Purif. 2019 Aug;160:73-83. doi: 10.1016/j.pep.2019.04.003. Epub 2019 Apr 17.
3
[Anti-prostate cancer activity of Survivin-T34A mutant in vitro and in vivo].Survivin-T34A突变体在体外和体内的抗前列腺癌活性
Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 May;41(3):390-3.
4
Procaspase 3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant-negative mutant, survivin T34A; a combination gene therapy strategy.卵巢癌细胞中procaspase 3的表达增加了生存素的转录，而这种情况可以通过一种显性负性突变体生存素T34A来对抗；这是一种联合基因治疗策略。
Oncogene. 2003 Jun 5;22(23):3539-47. doi: 10.1038/sj.onc.1206417.
5
Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells.Survivin靶向的黑色素瘤细胞中线粒体事件和非半胱天冬酶依赖性凋亡的快速诱导。
Oncogene. 2004 Jan 8;23(1):39-48. doi: 10.1038/sj.onc.1206978.
6
[Preparation of recombinant HIV-TATm-survivin (T34A) protein and its pro-apoptosis activity to cancer cells in vitro].重组HIV-TATm-生存素（T34A）蛋白的制备及其对癌细胞的体外促凋亡活性
Sheng Wu Gong Cheng Xue Bao. 2006 Mar;22(2):285-92. doi: 10.1016/s1872-2075(06)60028-9.
7
[Effects of Survivin-T34A mutant on breast cancer cell in vitro and in vivo].生存素-T34A突变体对乳腺癌细胞的体内外作用
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2014 Jun;31(3):648-51.
8
High-level expression, purification and pro-apoptosis activity of HIV-TAT-survivin (T34A) mutant to cancer cells in vitro.HIV-TAT-生存素（T34A）突变体在体外对癌细胞的高表达、纯化及促凋亡活性
J Biotechnol. 2006 May 29;123(3):367-78. doi: 10.1016/j.jbiotec.2005.11.018. Epub 2006 Jan 10.
9
Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response.生存素是凋亡抑制蛋白家族的成员之一，可由光动力疗法诱导产生，是改善治疗反应的一个靶点。
Cancer Res. 2007 May 15;67(10):4989-95. doi: 10.1158/0008-5472.CAN-06-4785.
10
Construction, expression, and purification of HIV-TAT-survivin (T34A) mutant: a pro-apoptosis protein in Escherichia coli.HIV-TAT-生存素（T34A）突变体在大肠杆菌中的构建、表达及纯化：一种促凋亡蛋白
Protein Expr Purif. 2006 May;47(1):36-44. doi: 10.1016/j.pep.2005.09.012. Epub 2005 Oct 11.

引用本文的文献

1
The potential of exosomes in regenerative medicine and in the diagnosis and therapies of neurodegenerative diseases and cancer.外泌体在再生医学以及神经退行性疾病和癌症的诊断与治疗中的潜力。
Front Med (Lausanne). 2025 Mar 13;12:1539714. doi: 10.3389/fmed.2025.1539714. eCollection 2025.
2
Exosome-Based Theranostic for Gastrointestinal Cancer: Advances in Biomarker Discovery and Therapeutic Engineering.基于外泌体的胃肠道癌诊疗：生物标志物发现与治疗工程进展
Small Methods. 2025 Feb 25:e2402058. doi: 10.1002/smtd.202402058.
3
Overcoming drug resistance through extracellular vesicle-based drug delivery system in cancer treatment.

本文引用的文献

1
Extracellular vesicles: biology and emerging therapeutic opportunities.细胞外囊泡：生物学和新兴的治疗机会。
Nat Rev Drug Discov. 2013 May;12(5):347-57. doi: 10.1038/nrd3978. Epub 2013 Apr 15.
2
Exosomes and communication between tumours and the immune system: are all exosomes equal?外泌体与肿瘤和免疫系统间的通讯：所有外泌体都一样吗？
Biochem Soc Trans. 2013 Feb 1;41(1):263-7. doi: 10.1042/BST20120245.
3
Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer.血浆衍生的外泌体生存素，前列腺癌早期检测的有前途的生物标志物。
癌症治疗中基于细胞外囊泡的药物递送系统克服耐药性
Cancer Drug Resist. 2024 Dec 12;7:50. doi: 10.20517/cdr.2024.107. eCollection 2024.
4
Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.揭开细胞外囊泡的秘密：调控肿瘤微环境在转移、耐药和免疫逃逸中的动态变化
J Cancer. 2024 Oct 14;15(19):6383-6415. doi: 10.7150/jca.98426. eCollection 2024.
5
Exosomes: from basic research to clinical diagnostic and therapeutic applications in cancer.外泌体：从基础研究到癌症的临床诊断与治疗应用
Cell Oncol (Dordr). 2025 Apr;48(2):269-293. doi: 10.1007/s13402-024-00990-2. Epub 2024 Sep 19.
6
Tumor-associated exosomes in cancer progression and therapeutic targets.肿瘤相关外泌体在癌症进展及治疗靶点中的作用
MedComm (2020). 2024 Sep 7;5(9):e709. doi: 10.1002/mco2.709. eCollection 2024 Sep.
7
Prospect of Gold Nanoparticles in Pancreatic Cancer.金纳米颗粒在胰腺癌中的应用前景
Pharmaceutics. 2024 Jun 14;16(6):806. doi: 10.3390/pharmaceutics16060806.
8
Alpha-hederin reprograms multi-miRNAs activity and overcome small extracellular vesicles-mediated paclitaxel resistance in NSCLC.α-常春藤皂苷元可重编程多种微小RNA的活性，并克服非小细胞肺癌中小细胞外囊泡介导的紫杉醇耐药性。
Front Pharmacol. 2024 Feb 1;15:1257941. doi: 10.3389/fphar.2024.1257941. eCollection 2024.
9
Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application.基于外泌体的肿瘤治疗递送策略：修饰、加载和临床应用的最新进展。
J Nanobiotechnology. 2024 Jan 28;22(1):41. doi: 10.1186/s12951-024-02298-7.
10
Exosomes: Emerging Modulators of Pancreatic Cancer Drug Resistance.外泌体：胰腺癌耐药性的新兴调节因子
Cancers (Basel). 2023 Sep 25;15(19):4714. doi: 10.3390/cancers15194714.
PLoS One. 2012;7(10):e46737. doi: 10.1371/journal.pone.0046737. Epub 2012 Oct 16.
4
Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies.卡铂和紫杉醇化疗联合静脉注射溶瘤单纯疱疹病毒治疗晚期恶性肿瘤的 I/II 期临床试验。
Clin Cancer Res. 2012 Apr 1;18(7):2080-9. doi: 10.1158/1078-0432.CCR-11-2181. Epub 2012 Feb 7.
5
Survivin knockdown enhances gastric cancer cell sensitivity to radiation and chemotherapy in vitro and in nude mice.Survivin 敲低增强胃癌细胞对体外和裸鼠体内放化疗的敏感性。
Am J Med Sci. 2012 Jul;344(1):52-8. doi: 10.1097/MAJ.0b013e318239c4ee.
6
RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer.RhoB 介导伊沙匹隆与舒尼替尼联合应用于人卵巢浆液性癌细胞的抗肿瘤协同作用。
Gynecol Oncol. 2012 Mar;124(3):589-97. doi: 10.1016/j.ygyno.2011.11.019. Epub 2011 Nov 22.
7
High expression of survivin predicts poor prognosis in esophageal squamous cell carcinoma following radiotherapy.生存素高表达预示食管鳞状细胞癌放疗后预后不良。
Tumour Biol. 2011 Dec;32(6):1147-53. doi: 10.1007/s13277-011-0217-y. Epub 2011 Aug 9.
8
Global cancer statistics.全球癌症统计数据。
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
9
Survivin-T34A: molecular mechanism and therapeutic potential.生存素-T34A：分子机制与治疗潜力
Onco Targets Ther. 2010 Dec 6;3:247-54. doi: 10.2147/OTT.S15293.
10
The application of exosomes as a nanoscale cancer vaccine.外泌体作为一种纳米级癌症疫苗的应用。
Int J Nanomedicine. 2010 Nov 10;5:889-900. doi: 10.2147/IJN.S13402.