聚氨酯三维肺癌模型的建立及姜黄素药敏试验
Establishment of Three-Dimensional Polyurethane Model of Lung Cancer and Curcumin Susceptibility Test
DOI: 10.12677/hjmce.2025.131002, PDF,    科研立项经费支持
作者: 王 晗：杭州医学院公共卫生学院，浙江 杭州；黄逸伦：温州医科大学阿尔伯塔学院，浙江 温州；朱 莲：杭州医学院基础医学与法医学院，浙江 杭州；张文元, 唐 靓*：杭州医学院检验医学院、生物工程学院，浙江 杭州
关键词: 聚氨酯泡沫；3D肺癌模型；姜黄素；药敏试验；Polyurethane Foam； 3D Lung Cancer Model； Curcumin； Drug Susceptibility Test
摘要: 目的：通过聚氨酯构建三维(3D)肺癌模型，并用于姜黄素药敏试验。方法：聚氨酯泡沫支架经I型胶原表面修饰后种植A549细胞构建肺癌3D模型，并进行姜黄素药敏试验。扫描电镜观察肺癌A549细胞生长情况。并均与2D培养下进行比较。结果：姜黄素可抑制A549的生长，浓度提高，抑制加强，呈剂量依赖性。3D培养条件下的细胞生长抑制率显著小于2D培养。结论：与2D培养相比，聚氨酯3D肺癌模型可能更好地模拟体内肺癌肿瘤微环境，提高临床前药物研究的预测能力，改善药物临床转化。
Abstract: Objective: To construct a three-dimensional (3D) lung cancer model by polyurethane and use it for curcumin drug sensitivity test. Methods: The 3D model of lung cancer was constructed by transplantation of A549 cells into polyurethane foam scaffolded with collagen type I surface modification, and curcumin susceptibility test was performed. The growth of lung cancer A549 cells was observed by scanning electron microscope. Then the results were compared with 2D culture. Results: Curcumin could inhibit the growth of A549. The concentration increased and the inhibition increased in a dose-dependent manner. The inhibition rate of 3D culture was significantly lower than that of 2D culture. Conclusion: Compared with 2D culture, polyurethane 3D lung cancer model may better simulate the microenvironment of lung cancer in vivo, and improve the predictive ability of preclinical drug studies, and improve the clinical transformation of drugs.
文章引用：王晗, 黄逸伦, 朱莲, 张文元, 唐靓. 聚氨酯三维肺癌模型的建立及姜黄素药敏试验[J]. 药物化学, 2025, 13(1): 11-18. https://doi.org/10.12677/hjmce.2025.131002

参考文献

[1] Lelli, D., Pedone, C., Majeed, M. and Sahebkar, A. (2017) Curcumin and Lung Cancer: The Role of MicroRNAs. Current Pharmaceutical Design, 23, 3440-3444. [Google Scholar] [CrossRef] [PubMed]
[2] Tzeng, Y.T., Hsiao, J., Tseng, L., Hou, M. and Li, C. (2023) Breast Cancer Organoids Derived from Patients: A Platform for Tailored Drug Screening. Biochemical Pharmacology, 217, Article 115803. [Google Scholar] [CrossRef] [PubMed]
[3] Bhattacharya, A., Alam, K., Roy, N.S., Kaur, K., Kaity, S., Ravichandiran, V., et al. (2023) Exploring the Interaction between Extracellular Matrix Components in a 3D Organoid Disease Model to Replicate the Pathophysiology of Breast Cancer. Journal of Experimental & Clinical Cancer Research, 42, Article No. 343. [Google Scholar] [CrossRef] [PubMed]
[4] Imamura, Y., Mukohara, T., Shimono, Y., Funakoshi, Y., Chayahara, N., Toyoda, M., et al. (2015) Comparison of 2D-and 3D-Culture Models as Drug-Testing Platforms in Breast Cancer. Oncology Reports, 33, 1837-1843. [Google Scholar] [CrossRef] [PubMed]
[5] Soflaei, S.S., Momtazi-Borojeni, A.A., Majeed, M., Derosa, G., Maffioli, P. and Sahebkar, A. (2018) Curcumin: A Natural Pan-HDAC Inhibitor in Cancer. Current Pharmaceutical Design, 24, 123-129. [Google Scholar] [CrossRef] [PubMed]
[6] Surh, Y. and Chun, K. (n.d.) Cancer Chemopreventive Effects of Curcumin. In: Aggarwal, B.B., Surh, YJ. and Shishodia, S., Eds., The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer, 149-172. [Google Scholar] [CrossRef] [PubMed]
[7] Ranjan, A.P., Mukerjee, A., Gdowski, A., Helson, L., Bouchard, A., Majeed, M., et al. (2016) Curcumin-ER Prolonged Subcutaneous Delivery for the Treatment of Non-Small Cell Lung Cancer. Journal of Biomedical Nanotechnology, 12, 679-688. [Google Scholar] [CrossRef] [PubMed]
[8] de Hoogt, R., Estrada, M.F., Vidic, S., Davies, E.J., Osswald, A., Barbier, M., et al. (2017) Protocols and Characterization Data for 2D, 3D, and Slice-Based Tumor Models from the PREDECT Project. Scientific Data, 4, Article No. 170170. [Google Scholar] [CrossRef] [PubMed]
[9] Barros, A.S., Costa, E.C., Nunes, A.S., de Melo-Diogo, D. and Correia, I.J. (2018) Comparative Study of the Therapeutic Effect of Doxorubicin and Resveratrol Combination on 2D and 3D (Spheroids) Cell Culture Models. International Journal of Pharmaceutics, 551, 76-83. [Google Scholar] [CrossRef] [PubMed]
[10] Zschenker, O., Streichert, T., Hehlgans, S. and Cordes, N. (2012) Genome-Wide Gene Expression Analysis in Cancer Cells Reveals 3D Growth to Affect ECM and Processes Associated with Cell Adhesion but Not DNA Repair. PLOS ONE, 7, e34279. [Google Scholar] [CrossRef] [PubMed]
[11] Pradhan, S., Clary, J.M., Seliktar, D. and Lipke, E.A. (2017) A Three-Dimensional Spheroidal Cancer Model Based on Peg-Fibrinogen Hydrogel Microspheres. Biomaterials, 115, 141-154. [Google Scholar] [CrossRef] [PubMed]
[12] Shafiee, A. and Atala, A. (2016) Printing Technologies for Medical Applications. Trends in Molecular Medicine, 22, 254-265. [Google Scholar] [CrossRef] [PubMed]
[13] Ghaemmaghami, A.M., Hancock, M.J., Harrington, H., Kaji, H. and Khademhosseini, A. (2012) Biomimetic Tissues on a Chip for Drug Discovery. Drug Discovery Today, 17, 173-181. [Google Scholar] [CrossRef] [PubMed]
[14] Li, Y. and Kilian, K.A. (2015) Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices. Advanced Healthcare Materials, 4, 2780-2796. [Google Scholar] [CrossRef] [PubMed]
[15] Brancato, V., Gioiella, F., Imparato, G., Guarnieri, D., Urciuolo, F. and Netti, P.A. (2018) 3D Breast Cancer Microtissue Reveals the Role of Tumor Microenvironment on the Transport and Efficacy of Free-Doxorubicin in vitro. Acta Biomaterialia, 75, 200-212. [Google Scholar] [CrossRef] [PubMed]
[16] Huerta-Reyes, M. and Aguilar-Rojas, A. (2021) Three-Dimensional Models to Study Breast Cancer (Review). International Journal of Oncology, 58, 331-343. [Google Scholar] [CrossRef] [PubMed]
[17] Milone, M.R., Pucci, B., Bruzzese, F., Carbone, C., Piro, G., Costantini, S., et al. (2013) Acquired Resistance to Zoledronic Acid and the Parallel Acquisition of an Aggressive Phenotype Are Mediated by P38-Map Kinase Activation in Prostate Cancer Cells. Cell Death & Disease, 4, e641-e641. [Google Scholar] [CrossRef] [PubMed]
[18] Yang, X., Gao, Y., Liu, Q., Wan, L., Liu, H., Bian, W., et al. (2020) Zoledronic Acid Re-Sensitises Gefitinib-Resistant Lung Cancer Cells by Inhibiting the JAK/STAT3 Signalling Pathway and Reversing Epithelial-Mesenchymal Transition. Oncology Reports, 45, 459-468. [Google Scholar] [CrossRef] [PubMed]
[19] Pereira, L.X., Viana, C.T.R., Orellano, L.A.A., Almeida, S.A., Vasconcelos, A.C., de Miranda Goes, A., et al. (2017) Synthetic Matrix of Polyether-Polyurethane as a Biological Platform for Pancreatic Regeneration. Life Sciences, 176, 67-74. [Google Scholar] [CrossRef] [PubMed]
[20] Shahrousvand, M., Sadeghi, G.M.M., Shahrousvand, E., Ghollasi, M. and Salimi, A. (2017) Superficial Physicochemical Properties of Polyurethane Biomaterials as Osteogenic Regulators in Human Mesenchymal Stem Cells Fates. Colloids and Surfaces B: Biointerfaces, 156, 292-304. [Google Scholar] [CrossRef] [PubMed]
[21] Totti, S., Allenby, M.C., Dos Santos, S.B., Mantalaris, A. and Velliou, E.G. (2018) A 3D Bioinspired Highly Porous Polymeric Scaffolding System for in Vitro Simulation of Pancreatic Ductal Adenocarcinoma. RSC Advances, 8, 20928-20940. [Google Scholar] [CrossRef] [PubMed]
[22] Asadpour, S., Ai, J., Davoudi, P., Ghorbani, M., Jalali Monfared, M. and Ghanbari, H. (2018) In vitro Physical and Biological Characterization of Biodegradable Elastic Polyurethane Containing Ferulic Acid for Small-Caliber Vascular Grafts. Biomedical Materials, 13, Article 035007. [Google Scholar] [CrossRef] [PubMed]
[23] Sun, L., Wang, X., He, Y., Chen, B., Shan, B., Yang, J., et al. (2023) Polyurethane Scaffold-Based 3D Lung Cancer Model Recapitulates in Vivo Tumor Biological Behavior for Nanoparticulate Drug Screening. Regenerative Biomaterials, 10, rbad091. [Google Scholar] [CrossRef] [PubMed]
[24] Tomeh, M.A., Hadianamrei, R. and Zhao, X. (2019) A Review of Curcumin and Its Derivatives as Anticancer Agents. International Journal of Molecular Sciences, 20, Article 1033. [Google Scholar] [CrossRef] [PubMed]
[25] Mirzaei, H., Bagheri, H., Ghasemi, F., Khoi, J.M., Pourhanifeh, M.H., Heyden, Y.V., et al. (2021) Anti-Cancer Activity of Curcumin on Multiple Myeloma. Anti-Cancer Agents in Medicinal Chemistry, 21, 575-586. [Google Scholar] [CrossRef] [PubMed]
[26] Devassy, J.G., Nwachukwu, I.D. and Jones, P.J.H. (2015) Curcumin and Cancer: Barriers to Obtaining a Health Claim. Nutrition Reviews, 73, 155-165. [Google Scholar] [CrossRef] [PubMed]
[27] Mehta, H.J., Patel, V. and Sadikot, R.T. (2014) Curcumin and Lung Cancer—A Review. Targeted Oncology, 9, 295-310. [Google Scholar] [CrossRef] [PubMed]
[28] Ji, J., Huang, X. and Zhu, H. (2012) Curcumin and Its Formulations: Potential Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry, 12, 210-218. [Google Scholar] [CrossRef] [PubMed]
[29] Rutz, J., Janicova, A., Woidacki, K., Chun, F.K.-H., Blaheta, R.A. and Relja, B. (2020) Curcumin—A Viable Agent for Better Bladder Cancer Treatment. International Journal of Molecular Sciences, 21, Article 3761. [Google Scholar] [CrossRef] [PubMed]