Camilla Carbone, Salvatrice Rigogliuso, Valerio Maria Bartolo Brucato, Alessandra Cusimano, Manuela Labbozzetta, Vincenzo La Carrubba, Paola Poma, Monica Notarbartolo, Francesco Carfì Pavia
{"title":"PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance","authors":"Camilla Carbone, Salvatrice Rigogliuso, Valerio Maria Bartolo Brucato, Alessandra Cusimano, Manuela Labbozzetta, Vincenzo La Carrubba, Paola Poma, Monica Notarbartolo, Francesco Carfì Pavia","doi":"10.1002/jbm.a.37836","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-<span>l</span>-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC<sub>50</sub> values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC<sub>50</sub> was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC<sub>50</sub>, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.</p>\n </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biomedical materials research. Part A","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.37836","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-l-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC50 values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC50 was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC50, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.
期刊介绍:
The Journal of Biomedical Materials Research Part A is an international, interdisciplinary, English-language publication of original contributions concerning studies of the preparation, performance, and evaluation of biomaterials; the chemical, physical, toxicological, and mechanical behavior of materials in physiological environments; and the response of blood and tissues to biomaterials. The Journal publishes peer-reviewed articles on all relevant biomaterial topics including the science and technology of alloys,polymers, ceramics, and reprocessed animal and human tissues in surgery,dentistry, artificial organs, and other medical devices. The Journal also publishes articles in interdisciplinary areas such as tissue engineering and controlled release technology where biomaterials play a significant role in the performance of the medical device.
The Journal of Biomedical Materials Research is the official journal of the Society for Biomaterials (USA), the Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials.
Articles are welcomed from all scientists. Membership in the Society for Biomaterials is not a prerequisite for submission.