癌症细胞球体作为评估化疗方案的模型。
Cancer cell spheroids as a model to evaluate chemotherapy protocols.
机构信息
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
出版信息
Cancer Biol Ther. 2012 Oct;13(12):1205-13. doi: 10.4161/cbt.21353. Epub 2012 Aug 15.
Abstract
To determine whether the spheroid culture can be used to evaluate drug efficacy, we have evaluated the toxicity of free or carrier-associated doxorubicin as a single drug or in combination with other antineoplastic agents using the spheroid cultures of drug-resistant cancer cells. Paclitaxel, cisplatin, dexamethasone, mitoxantrone, sclareol or methotrexate were used in combination with doxorubicin. The effect of the treatment protocols on free, micellar and liposomal doxorubicin accumulation in spheroids and on resulting toxicity was evaluated by fluorescence and lactate dehydrogenase release, respectively. Enhanced doxorubicin accumulation and toxicity were observed after spheroid pretreatment with mitoxantrone or paclitaxel. Effects of the drug combination with doxorubicin were sequence dependent, use of doxorubicin as the first drug being the least inducer of toxicity. Finally, spheroids were recognized by a cancer cell-specific antibody. Our results suggest the usefulness of spheroids to evaluate chemotherapy combinations.
摘要
为了确定球体培养是否可用于评估药物疗效，我们使用耐药癌细胞的球体培养物评估了游离或载体结合的阿霉素作为单一药物或与其他抗肿瘤药物联合使用的毒性。紫杉醇、顺铂、地塞米松、米托蒽醌、青蒿醇或甲氨蝶呤与阿霉素联合使用。通过荧光和乳酸脱氢酶释放分别评估治疗方案对球体中游离、胶束和脂质体阿霉素积累以及由此产生的毒性的影响。在用米托蒽醌或紫杉醇预处理球体后，观察到阿霉素的积累和毒性增强。药物组合与阿霉素的作用具有序列依赖性，将阿霉素作为第一种药物使用时毒性最小。最后，用一种癌细胞特异性抗体识别球体。我们的结果表明，球体可用于评估化疗组合。
相似文献
1
Cancer cell spheroids as a model to evaluate chemotherapy protocols.癌症细胞球体作为评估化疗方案的模型。
Cancer Biol Ther. 2012 Oct;13(12):1205-13. doi: 10.4161/cbt.21353. Epub 2012 Aug 15.
2
Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model.抗体靶向载多柔比星 PEG-PE 胶束在卵巢癌细胞球模型中的积累和毒性。
J Control Release. 2012 Nov 28;164(1):95-102. doi: 10.1016/j.jconrel.2012.09.003. Epub 2012 Sep 10.
3
Nanomedicine based curcumin and doxorubicin combination treatment of glioblastoma with scFv-targeted micelles: In vitro evaluation on 2D and 3D tumor models.基于纳米医学的姜黄素与阿霉素联合治疗胶质母细胞瘤：单链抗体靶向胶束的二维和三维肿瘤模型体外评价
Eur J Pharm Biopharm. 2016 Nov;108:54-67. doi: 10.1016/j.ejpb.2016.08.013. Epub 2016 Aug 26.
4
Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation.多柔比星增强复合胶束包封的肺癌细胞系多层球体的放射敏感性。
Int J Nanomedicine. 2012;7:2661-71. doi: 10.2147/IJN.S30445. Epub 2012 May 29.
5
Antitumor drug delivery in multicellular spheroids by electropermeabilization.多细胞球体中的电穿孔法递送抗肿瘤药物。
J Control Release. 2013 Apr 28;167(2):138-47. doi: 10.1016/j.jconrel.2013.01.021. Epub 2013 Feb 4.
6
Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in patients with advanced solid tumors.聚乙二醇化脂质体阿霉素、紫杉醇和顺铂用于晚期实体瘤患者的I期研究。
Ann Oncol. 2001 Dec;12(12):1743-7. doi: 10.1023/a:1013574328938.
7
Enhanced targeting of 3D pancreatic cancer spheroids by aptamer-conjugated polymeric micelles with deep tumor penetration.适体偶联聚合物胶束通过深层肿瘤渗透增强对 3D 胰腺癌球体的靶向性。
Eur J Pharmacol. 2021 Mar 5;894:173814. doi: 10.1016/j.ejphar.2020.173814. Epub 2020 Dec 19.
8
Doxorubicin and α-Mangostin oppositely affect luminal breast cancer cell stemness evaluated by a new retinaldehyde-dependent ALDH assay in MCF-7 tumor spheroids.阿霉素和α-倒捻子素通过新的视黄醛依赖性 ALDH 测定法在 MCF-7 肿瘤球体中对腔型乳腺癌细胞干性的相反影响。
Biomed Pharmacother. 2020 Apr;124:109927. doi: 10.1016/j.biopha.2020.109927. Epub 2020 Jan 23.
9
Pharmaceutical and biomedical differences between micellar doxorubicin (NK911) and liposomal doxorubicin (Doxil).胶束阿霉素（NK911）与脂质体阿霉素（多柔比星脂质体）之间的药物及生物医学差异
Jpn J Cancer Res. 2002 Oct;93(10):1145-53. doi: 10.1111/j.1349-7006.2002.tb01217.x.
10
Comparative study of the therapeutic effect of Doxorubicin and Resveratrol combination on 2D and 3D (spheroids) cell culture models.多柔比星和白藜芦醇联合治疗对 2D 和 3D（球体）细胞培养模型的疗效比较研究。
Int J Pharm. 2018 Nov 15;551(1-2):76-83. doi: 10.1016/j.ijpharm.2018.09.016. Epub 2018 Sep 11.
引用本文的文献
1
A modular and reconfigurable microfluidic device for culturing spheroids under continuous perfusion.一种用于在连续灌注条件下培养球体的模块化可重构微流控装置。
APL Bioeng. 2025 Aug 13;9(3):036111. doi: 10.1063/5.0262536. eCollection 2025 Sep.
2
Size-dependent invasion and therapeutic phenotype of 42MGBA glioblastoma spheroids.42MGBA胶质母细胞瘤球体的大小依赖性侵袭和治疗表型
bioRxiv. 2025 Aug 6:2025.07.09.663980. doi: 10.1101/2025.07.09.663980.
3
Three-Dimensional Culture System: A New Frontier in Cancer Research, Drug Discovery, and Stem Cell-Based Therapy.三维培养系统：癌症研究、药物发现及基于干细胞治疗的新前沿
Biology (Basel). 2025 Jul 17;14(7):875. doi: 10.3390/biology14070875.
4
Numerical modeling of oxygen diffusion in tissue spheroids undergoing fusion using function representation and finite volumes.使用函数表示法和有限体积法对正在融合的组织球状体中的氧气扩散进行数值模拟。
Sci Rep. 2025 Feb 11;15(1):5054. doi: 10.1038/s41598-025-86805-2.
5
Establishment and characterization of a novel patient-derived cell line from conventional central grade 3 chondrosarcoma, NCC-CS1-C1.源自传统中央型3级软骨肉瘤的新型患者源细胞系NCC-CS1-C1的建立与鉴定
Hum Cell. 2024 Dec 8;38(1):28. doi: 10.1007/s13577-024-01152-0.
6
Establishment and characterization of NCC-GCTB14-C1 and NCC-GCTB15-C1: two novel patient-derived cell lines of giant cell tumor of bone.建立并鉴定 NCC-GCTB14-C1 和 NCC-GCTB15-C1：两种新型的骨巨细胞瘤患者来源细胞系。
Hum Cell. 2024 Nov 27;38(1):20. doi: 10.1007/s13577-024-01150-2.
7
A high-throughput microfabricated platform for rapid quantification of metastatic potential.高通量微制造平台，用于快速定量分析转移潜能。
Sci Adv. 2024 Aug 16;10(33):eadk0015. doi: 10.1126/sciadv.adk0015.
8
Fabrication and Evaluation of PCL/PLGA/β-TCP Spiral-Structured Scaffolds for Bone Tissue Engineering.用于骨组织工程的聚己内酯/聚乳酸-羟基乙酸共聚物/β-磷酸三钙螺旋结构支架的制备与评价
Bioengineering (Basel). 2024 Jul 19;11(7):732. doi: 10.3390/bioengineering11070732.
9
A Comprehensive Characterization of a New Class of Indole-Based Compounds Developed as Selective Haspin Inhibitors.一类作为选择性Haspin抑制剂开发的新型吲哚类化合物的全面表征
J Med Chem. 2024 Aug 8;67(15):12711-12734. doi: 10.1021/acs.jmedchem.4c00718. Epub 2024 Jul 22.
10
Integrin-linked kinase-frizzled 7 interaction maintains cancer stem cells to drive platinum resistance in ovarian cancer.整合素连接激酶-卷曲蛋白 7 相互作用维持癌症干细胞，从而导致卵巢癌对铂类耐药。
J Exp Clin Cancer Res. 2024 Jun 1;43(1):156. doi: 10.1186/s13046-024-03083-y.
本文引用的文献
1
Mitoxantrone targets the ATP-binding site of FAK, binds the FAK kinase domain and decreases FAK, Pyk-2, c-Src, and IGF-1R in vitro kinase activities.米托蒽醌靶向 FAK 的 ATP 结合位点，结合 FAK 激酶结构域，并降低 FAK、Pyk-2、c-Src 和 IGF-1R 的体外激酶活性。
Anticancer Agents Med Chem. 2013 May;13(4):546-54. doi: 10.2174/1871520611313040003.
2
Targeted inhibition of telomerase activity combined with chemotherapy demonstrates synergy in eliminating ovarian cancer spheroid-forming cells.靶向抑制端粒酶活性联合化疗在消除卵巢癌球体形成细胞中表现出协同作用。
Gynecol Oncol. 2012 Mar;124(3):598-605. doi: 10.1016/j.ygyno.2011.11.018. Epub 2011 Nov 22.
3
Improving delivery and efficacy of nanomedicines in solid tumors: role of tumor priming.提高实体瘤中纳米药物的递送和疗效：肿瘤引发作用。
Nanomedicine (Lond). 2011 Nov;6(9):1605-20. doi: 10.2217/nnm.11.141.
4
Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy.预处理线粒体预刺激与细胞毒性化疗的临床反应相关。
Science. 2011 Nov 25;334(6059):1129-33. doi: 10.1126/science.1206727. Epub 2011 Oct 27.
5
How to improve exposure of tumor cells to drugs: promoter drugs increase tumor uptake and penetration of effector drugs.如何提高肿瘤细胞对药物的暴露程度：启动药物可增加效应药物在肿瘤中的摄取和穿透。
Adv Drug Deliv Rev. 2012 Jan;64(1):53-68. doi: 10.1016/j.addr.2011.09.007. Epub 2011 Sep 29.
6
Pharmacological basis of pegylated liposomal doxorubicin: impact on cancer therapy.聚乙二醇脂质体阿霉素的药理学基础：对癌症治疗的影响。
Eur J Pharm Sci. 2012 Mar 12;45(4):388-98. doi: 10.1016/j.ejps.2011.09.006. Epub 2011 Sep 10.
7
Mitoxantrone inhibits HIF-1α expression in a topoisomerase II-independent pathway.米托蒽醌通过一种拓扑异构酶 II 非依赖的途径抑制 HIF-1α 的表达。
Clin Cancer Res. 2011 Aug 1;17(15):5026-37. doi: 10.1158/1078-0432.CCR-11-0235. Epub 2011 Jun 8.
8
Paclitaxel tumor-priming enhances siRNA delivery and transfection in 3-dimensional tumor cultures.紫杉醇肿瘤引发增强了三维肿瘤培养中的 siRNA 传递和转染。
Mol Pharm. 2011 Jun 6;8(3):833-40. doi: 10.1021/mp1004383. Epub 2011 Mar 29.
9
Accumulation and distribution of doxorubicin in tumour spheroids: the influence of acidity and expression of P-glycoprotein.阿霉素在肿瘤球体中的积累和分布：酸度和 P-糖蛋白表达的影响。
Cancer Chemother Pharmacol. 2011 Nov;68(5):1179-90. doi: 10.1007/s00280-011-1598-8. Epub 2011 Mar 15.
10
The delivery of doxorubicin to 3-D multicellular spheroids and tumors in a murine xenograft model using tumor-penetrating triblock polymeric micelles.使用穿透肿瘤的嵌段聚合物胶束向 3-D 多细胞球体和小鼠异种移植模型中的肿瘤递送阿霉素。
Biomaterials. 2010 Oct;31(28):7386-97. doi: 10.1016/j.biomaterials.2010.06.004. Epub 2010 Jul 3.
Zotero 插件