靶向 90kDa 热休克蛋白可提高光动力疗法效果。
Targeting the 90 kDa heat shock protein improves photodynamic therapy.
机构信息
The Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
出版信息
Cancer Lett. 2010 Mar 28;289(2):188-94. doi: 10.1016/j.canlet.2009.08.015. Epub 2009 Sep 3.
Abstract
The geldanamycin derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), binds to the amino-terminal ATP binding pocket of the 90 kDa heat shock protein (Hsp-90) and inhibits this chaperone from stabilizing client proteins involved with the malignant phenotype. We examined the effects of a combined modality protocol involving photodynamic therapy (PDT) and 17-AAG in mouse mammary carcinoma cells and tumors. PDT increased the expression of the anti-apoptotic and pro-angiogenic proteins survivin, Akt, HIF-1alpha, MMP-2 and VEGF in tumor tissue and this expression decreased significantly when 17-AAG was included in the treatment regimen. Tumor bearing mice treated with PDT and 17-AAG had improved long-term tumoricidal responses when compared with individual treatment protocols. We conclude that Hsp-90 plays an active role in modulating tumor responsiveness following PDT and targeting Hsp-90 with 17-AAG enhances the therapeutic effectiveness of PDT.
摘要
格尔德霉素衍生物 17-烯丙氨基-17-去甲氧基格尔德霉素（17-AAG）与 90kDa 热休克蛋白（Hsp-90）的氨基末端 ATP 结合口袋结合，并抑制该伴侣蛋白稳定与恶性表型相关的客户蛋白。我们研究了包括光动力疗法（PDT）和 17-AAG 的联合治疗方案在小鼠乳腺癌细胞和肿瘤中的作用。PDT 增加了肿瘤组织中抗凋亡和促血管生成蛋白生存素、Akt、HIF-1α、MMP-2 和 VEGF 的表达，而当 17-AAG 包含在治疗方案中时，这种表达显著下降。与单独的治疗方案相比，接受 PDT 和 17-AAG 治疗的荷瘤小鼠具有更好的长期抗肿瘤反应。我们得出结论，Hsp-90 在调节 PDT 后的肿瘤反应中起积极作用，用 17-AAG 靶向 Hsp-90 可增强 PDT 的治疗效果。
相似文献
1
Targeting the 90 kDa heat shock protein improves photodynamic therapy.靶向 90kDa 热休克蛋白可提高光动力疗法效果。
Cancer Lett. 2010 Mar 28;289(2):188-94. doi: 10.1016/j.canlet.2009.08.015. Epub 2009 Sep 3.
2
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.
3
Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness.绿茶成分表没食子儿茶素没食子酸酯的促凋亡和抗炎特性增强了光动力疗法的反应性。
Lasers Surg Med. 2011 Sep;43(7):644-50. doi: 10.1002/lsm.21081.
4
Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEU-NT mice monitored by Magnetic Resonance Spectroscopy.热休克蛋白90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）对通过磁共振波谱监测的MMTV-NEU-NT小鼠中NEU/HER2过表达乳腺肿瘤的影响。
BMC Res Notes. 2012 May 23;5:250. doi: 10.1186/1756-0500-5-250.
5
Induction of prosurvival molecules during treatment: rethinking therapy options for photodynamic therapy.诱导治疗期间的生存相关分子：重新思考光动力疗法的治疗选择。
J Natl Compr Canc Netw. 2012 Oct 1;10 Suppl 2:S35-9. doi: 10.6004/jnccn.2012.0172.
6
Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.热休克蛋白90抑制剂可降低瘢痕疙瘩成纤维细胞的胶原蛋白合成，并在瘢痕疙瘩球体模型上减轻细胞外基质。
Plast Reconstr Surg. 2015 Sep;136(3):328e-337e. doi: 10.1097/PRS.0000000000001538.
7
17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.17-AAG抑制维莫非尼相关的丝裂原活化蛋白激酶激活，并在小鼠黑色素瘤模型中与细胞免疫疗法具有协同作用。
PLoS One. 2018 Feb 26;13(2):e0191264. doi: 10.1371/journal.pone.0191264. eCollection 2018.
8
Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma.抗血管生成治疗可增强小鼠乳腺癌对光动力疗法的反应性。
Cancer Res. 2000 Aug 1;60(15):4066-9.
9
ATP analog enhances the actions of a heat shock protein 90 inhibitor in multiple myeloma cells.三磷酸核苷类似物增强热休克蛋白 90 抑制剂在多发性骨髓瘤细胞中的作用。
J Pharmacol Exp Ther. 2011 Nov;339(2):545-54. doi: 10.1124/jpet.111.184903. Epub 2011 Aug 5.
10
Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo.热休克蛋白90的抑制作用会损害胃癌细胞中表皮生长因子介导的信号传导，并在体内减少肿瘤生长和血管生成。
Mol Cancer Ther. 2007 Mar;6(3):1123-32. doi: 10.1158/1535-7163.MCT-06-0628.
引用本文的文献
1
Lipid-Coated Ag@MnO Core-Shell Nanoparticles for Co-Delivery of Survivin siRNA in Breast Tumor Therapy.用于乳腺癌治疗中Survivin siRNA共递送的脂质包被Ag@MnO核壳纳米颗粒
Int J Nanomedicine. 2025 May 22;20:6515-6531. doi: 10.2147/IJN.S510514. eCollection 2025.
2
Modulation of heat shock protein expression and cytokine levels in MCF-7 cells through photodynamic therapy.通过光动力疗法调节 MCF-7 细胞中的热休克蛋白表达和细胞因子水平。
Lasers Med Sci. 2024 May 24;39(1):135. doi: 10.1007/s10103-024-04092-1.
3
Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci and .热休克蛋白抑制剂与光动力疗法联合应用对致龋链球菌具有协同抗菌作用 。
mSphere. 2023 Apr 20;8(2):e0067922. doi: 10.1128/msphere.00679-22. Epub 2023 Feb 28.
4
A J-aggregated nanoporphyrin overcoming phototoxic side effects in superior phototherapy with two-pronged effects.一种J-聚集纳米卟啉在具有双管齐下作用的高级光疗中克服光毒性副作用。
Chem Sci. 2022 Oct 15;13(43):12738-12746. doi: 10.1039/d2sc04873f. eCollection 2022 Nov 9.
5
Emerging photodynamic/sonodynamic therapies for urological cancers: progress and challenges.新兴的光动力/声动力疗法治疗泌尿系统癌症：进展与挑战。
J Nanobiotechnology. 2022 Oct 4;20(1):437. doi: 10.1186/s12951-022-01637-w.
6
Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.抑制 HIF-1 生存通路作为增强光动力疗法疗效的策略。
Methods Mol Biol. 2022;2451:285-403. doi: 10.1007/978-1-0716-2099-1_19.
7
Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells.没食子酸表没食子儿茶素酯增强 MAL-PDT 对光动力疗法耐药皮肤鳞状细胞癌细胞的细胞毒性作用。
Int J Mol Sci. 2020 May 8;21(9):3327. doi: 10.3390/ijms21093327.
8
The Role of Erythroid Differentiation Regulator 1 (ERDR1) in the Control of Proliferation and Photodynamic Therapy (PDT) Response.红细胞分化调控因子 1（ERDR1）在增殖控制和光动力疗法（PDT）反应中的作用。
Int J Mol Sci. 2020 Apr 9;21(7):2603. doi: 10.3390/ijms21072603.
9
Image-guided photo-therapeutic nanoporphyrin synergized HSP90 inhibitor in patient-derived xenograft bladder cancer model.基于影像引导的光热治疗卟啉与热休克蛋白 90 抑制剂协同作用于患者来源的膀胱癌异种移植模型。
Nanomedicine. 2018 Apr;14(3):789-799. doi: 10.1016/j.nano.2017.12.014. Epub 2018 Jan 6.
10
Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins.通过靶向热休克蛋白90相关蛋白改善金丝桃素的光动力疗法
Pharmaceuticals (Basel). 2011 Nov 10;4(11):1488-1502. doi: 10.3390/ph4111488.
本文引用的文献
1
Heat shock protein 90 as a drug target: some like it hot.热休克蛋白90作为一种药物靶点：有人喜欢它的热度。
Clin Cancer Res. 2009 Jan 1;15(1):9-14. doi: 10.1158/1078-0432.CCR-08-0132.
2
A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer.17-烯丙基氨基-17-去甲氧基格尔德霉素用于激素难治性转移性前列腺癌患者的II期试验。
Clin Cancer Res. 2008 Dec 1;14(23):7940-6. doi: 10.1158/1078-0432.CCR-08-0221.
3
An in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models.热休克蛋白抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素与卡铂联合应用于人类卵巢癌模型的体外和体内研究。
Cancer Chemother Pharmacol. 2008 Oct;62(5):769-78. doi: 10.1007/s00280-007-0662-x. Epub 2008 Jan 10.
4
Multiple components of photodynamic therapy can phosphorylate Akt.光动力疗法的多个成分可使Akt磷酸化。
Photochem Photobiol. 2007 Sep-Oct;83(5):1029-33. doi: 10.1111/j.1751-1097.2007.00137.x.
5
Apoptosis and autophagy after mitochondrial or endoplasmic reticulum photodamage.线粒体或内质网光损伤后的细胞凋亡与自噬
Photochem Photobiol. 2007 Sep-Oct;83(5):1024-8. doi: 10.1111/j.1751-1097.2007.00088.x.
6
Strategies for enhanced photodynamic therapy effects.增强光动力治疗效果的策略。
Photochem Photobiol. 2007 Sep-Oct;83(5):996-1005. doi: 10.1111/j.1751-1097.2007.00166.x.
7
Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis.细胞外热休克蛋白90：分子伴侣在细胞运动性和癌症转移中的作用
Cancer Sci. 2007 Oct;98(10):1536-9. doi: 10.1111/j.1349-7006.2007.00561.x. Epub 2007 Jul 23.
8
Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress.靶向癌症伴侣蛋白HSP90：癌基因成瘾与肿瘤应激的联合治疗应用
Ann N Y Acad Sci. 2007 Oct;1113:202-16. doi: 10.1196/annals.1391.012. Epub 2007 May 18.
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
Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with refractory advanced cancers.17-（烯丙基氨基）-17-去甲氧基格尔德霉素在难治性晚期癌症成年患者中的I期及药效学研究。
Clin Cancer Res. 2007 Mar 15;13(6):1769-74. doi: 10.1158/1078-0432.CCR-06-2233.
Zotero 插件