A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay
Open accessAbstract
Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.
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Cells in the spheroid-based 3D model exhibit higher drug resistance during drug testing than cells in the monolayer model.
“Compared with those in the monolayer model, the cells in the spheroid-based 3D model exhibit higher drug resistance during drug testing, and the 3D model is closer to the chemical environment of native tissues215.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [215]
The spheroid-based 3D model is closer to the chemical environment of native tissues than the monolayer model.
“Compared with those in the monolayer model, the cells in the spheroid-based 3D model exhibit higher drug resistance during drug testing, and the 3D model is closer to the chemical environment of native tissues215.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [215]
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Cites
Capturing complex 3D tissue physiology in vitro
Griffith, L. G., & Swartz, M. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1858 · Cited by 2,274 · see citing works
Spheroid-based drug screen: Considerations and practical approach
Friedrich, J., Seidel, C., Ebner, R., & Kunz-Schughart, L. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.226 · Cited by 1,742 · see citing works
Multicellular tumor spheroids: An underestimated tool is catching up again
Hirschhaeuser, F., Menne, H., Dittfeld, C., West, J., Mueller-Klieser, W., & Kunz-Schughart, L. A. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.01.012 · Cited by 1,674 · see citing works
Epithelial to Mesenchymal Transition Contributes to Drug Resistance in Pancreatic Cancer
Arumugam, T., Ramachandran, V., Fournier, K. F., Wang, H., Marquis, L., Abbruzzese, J. L., Gallick, G. E., Logsdon, C. D., McConkey, D. J., & Choi, W. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2819 · Cited by 866 · see citing works
The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.
Kunz-Schughart, L. A., Freyer, J. P., Hofstaedter, F., & Ebner, R. (2004) · SLAS DISCOVERY · doi:10.1177/1087057104265040 · Cited by 797 · see citing works
Mikos, A. G., Herring, S. W., Ochareon, P., Elisseeff, J. H., Lu, H. H., Kandel, R. A., Schöen, F. J., Toner, M., Mooney, D. J., Atala, A., et al. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.3307 · Cited by 594 · see citing works
Growth of Multicell Spheroids in Tissue Culture as a Model of Nodular Carcinomas 2
Sutherland, R. M., McCredie, J. A., & Inch, W. R. (1971) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/46.1.113 · Cited by 585 · see citing works
Therapeutic implications of cancer stem cells
Al‐Hajj, M., Becker, M. W., Wicha, M. S., Weissman, I. L., & Clarke, M. F. (2003) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2003.11.007 · Cited by 561 · see citing works
A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies
Elliott, N. T., & Yuan, F. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22257 · Cited by 449 · see citing works
Experimental anti-tumor therapy in 3-D: Spheroids – old hat or new challenge?
Friedrich, J., Ebner, R., & Kunz‐Schughart, L. A. (2007) · International Journal of Radiation Biology · doi:10.1080/09553000701727531 · Cited by 445 · see citing works
Development and Characterization of Gemcitabine-Resistant Pancreatic Tumor Cells
Shah, A. N., Summy, J. M., Zhang, J., Park, S. I., Parikh, N. U., & Gallick, G. E. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9583-5 · Cited by 434 · see citing works
Multicellular spheroids in ovarian cancer metastases: Biology and pathology
Shield, K., Ackland, M. L., Ahmed, N., & Rice, G. E. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.11.032 · Cited by 412 · see citing works
Multicellular resistance: a paradigm for clinical resistance?
Desoize, B. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00086-x · Cited by 400 · see citing works
Radiation response of multicell spheroids--an in vitro tumour model.
Rm, S., & Re, D. (1976) · PubMed · Cited by 232 · see citing works
A reliable tool to determine cell viability in complex 3-d culture: the acid phosphatase assay
Friedrich, J., Eder, W., Castaneda, J., Doss, M., Huber, E., Ebner, R., & Kunz-Schughart, L. A. (2007) · SLAS DISCOVERY · doi:10.1177/1087057107306839 · Cited by 227 · see citing works
Stress Clamp Experiments on Multicellular Tumor Spheroids
Montel, F., Delarue, M., Elgeti, J., Malaquin, L., Basan, M., Risler, T., Cabane, B., Vignjevic, D. M., Prost, J., Cappello, G., et al. (2011) · Physical Review Letters · doi:10.1103/physrevlett.107.188102 · Cited by 219 · see citing works
Khaitan, D., Chandna, S., Arya, M., & Dwarakanath, B. (2006) · Journal of Translational Medicine · doi:10.1186/1479-5876-4-12 · Cited by 196 · see citing works
Engineering Tumors: A Tissue Engineering Perspective in Cancer Biology
Burdett, E., Kasper, F. K., Mikos, A. G., & Ludwig, J. A. (2010) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2009.0676 · Cited by 173 · see citing works
Akada, M., Crnogorac‐Jurcevic, T., Lattimore, S., Mahon, P. C., Lopes, R., Sunamura, M., Matsuno, S., & Lemoine, N. R. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1785 · Cited by 168 · see citing works
Barbone, D., Yang, T., Morgan, J. R., Gaudino, G., & Broaddus, V. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709698200 · Cited by 148 · see citing works
Drewitz, M., Helbling, M. M., Fried, N., Bieri, M., Moritz, W., Lichtenberg, J., & Kelm, J. M. (2011) · Biotechnology Journal · doi:10.1002/biot.201100290 · Cited by 124 · see citing works
Ho, W. J., Pham, E. A., Kim, J. W., Ng, C. W., Kim, J. H., Kamei, D. T., & Wu, B. M. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01723.x · Cited by 115 · see citing works
Invited review Multicell spheroids as a model for cell kinetic studies
Durand, R. E. (1990) · Cell Proliferation · doi:10.1111/j.1365-2184.1990.tb01111.x · Cited by 89 · see citing works
Enmon, R. M., Yang, W.-H., Ballangrud, Å., Solit, D. B., Heller, G., Rosen, N. X., Scher, H. I., & Sgouros, G. (2003) · PubMed · Cited by 66 · see citing works
Tibben, J. G., Boerman, O. C., Massuger, L. F. A. G., Schijf, C. P. T., Claessens, R. A. M. J., & Corstens, F. H. M. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960516)66:4 · Cited by 60 · see citing works
Evaluation of bioreductive drugs in multicell spheroids
Durand, R. E., & Olive, P. L. (1992) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(92)90504-b · Cited by 54 · see citing works
Sempere, L. F., Gunn, J. R., & Korc, M. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.12.3.15979 · Cited by 52 · see citing works
Cichon, M. A., Gainullin, V. G., Zhang, Y., & Radisky, D. C. (2011) · Integrative Biology · doi:10.1039/c1ib00090j · Cited by 40 · see citing works
Fujita, H. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1058 · Cited by 37 · see citing works
Groebe, K., Erz, S., & Mueller‐Klieser, W. (1994) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-1875-4_114 · Cited by 36 · see citing works
Adjuvant treatment of pancreatic cancer
Neoptolemos, J. P. (2011) · European Journal of Cancer · doi:10.1016/s0959-8049(11)70210-6 · Cited by 30 · see citing works
Multicellular tumor spheroid formation in duplex microcapsules for analysis of chemosensitivity
Sakai, S., Inamoto, K., Liu, Y., Tanaka, S., Arii, S., & Taya, M. (2011) · Cancer Science · doi:10.1111/j.1349-7006.2011.02187.x · Cited by 27 · see citing works
Fehlauer, F., Muench, M., Rades, D., et al. (2005) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-005-0014-3 · Cited by 24 · see citing works
Lambert, B., Ridder, L. D., Slegers, G., et al. (2004) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y04-008 · Cited by 19 · see citing works
Kruttwig, K., Brueggemann, C., Kaijzel, E. L., Vorhagen, S., Hilger, T., Löwik, C. W. G. M., & Hoehn, M. (2009) · Molecular Imaging and Biology · doi:10.1007/s11307-009-0289-x · Cited by 15 · see citing works
Multicellular Tumor Spheroids Grown from Pancreatic Carcinoma Cell Lines
McLeod, E. J., Beischer, A. D., Hill, J. S., et al. (1997) · Pancreas · doi:10.1097/00006676-199704000-00004 · Cited by 11 · see citing works
Assessment of pancreatic carcinoma cell chemosensitivity using a three-dimensional culture system.
Liao, Q., Hu, Y., Zhao, Y.-P., et al. (2010) · PubMed · Cited by 10 · see citing works
Self-citationZhang, Q., Zhao, Y.-P., Liao, Q., et al. (2011) · PubMed · Cited by 8 · see citing works
Self-citationDynamics of Cell Kinetic Parameters During 9l Spheroid Growth
Sweigert, S. E., & Alpen, E. L. (1986) · Cell Proliferation · doi:10.1111/j.1365-2184.1986.tb00757.x · Cited by 6 · see citing works
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Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Lazzari, G., Nicolas, V., Matsusaki, M., Akashi, M., Couvreur, P., & Mura, S. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.08.008 · Cited by 271 · see citing works
Tumor-on-a-chip: from bioinspired design to biomedical application
Liu, X., Fang, J., Huang, S., Wu, X., Xie, X., Wang, J., Liu, F., Zhang, M., Peng, Z., & Hu, N. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00277-8 · Cited by 246 · see citing works
Colorectal tumor-on-a-chip system: a 3D tool for precision onco-nanomedicine
Carvalho, M. R., Barata, D., Teixeira, L. M., Giselbrecht, S., Reis, R. L., Oliveira, J. M., Truckenmüller, R., & Habibovic, P. (2019) · Science Advances · doi:10.1126/sciadv.aaw1317 · Cited by 230 · see citing works
Costa, E. C., de Melo‐Diogo, D., Moreira, A. F., Carvalho, M. P., & Correia, I. J. (2018) · Biotechnology Journal · doi:10.1002/biot.201700417 · Cited by 224 · see citing works
Ranjbar-Mohammadi, M., Abbasian, M., Mousavi, E., & Arab-Bafrani, Z. (2019) · European Polymer Journal · doi:10.1016/j.eurpolymj.2019.03.024 · Cited by 26 · see citing works
- Authors
- Wen, Z., Liao, Q., Hu, Y., You, L., Zhou, L., & Zhao, Y.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Venue
- Brazilian Journal of Medical and Biological Research
- Publisher
- FapUNIFESP (SciELO)
- Published
- 2013-07
- Volume
- 46
- Issue
- 7
- Pages
- 634-642
- ISSN
- 0100-879X (ISSN-L)
- PMC
- PMC3859338
- OpenAlex
- W2149006989
- Cited by
- 102
- References
- 39
- Citations by year
- 2026: 1 · 2025: 13 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 13 · 2019: 15 · 2018: 7 · 2017: 10 · 2016: 8 · 2014: 5
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Brazilian Journal of Medical and Biological Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- pancreatic cancer, spheroid culture, 3D cell culture, drug testing, MIA PaCa-2 cells, PANC-1 cells, drug resistance, tumor microenvironment, in vitro drug testing
- MeSH terms
- Gemcitabine, Acid Phosphatase, Antimetabolites, Antineoplastic, Cell Survival, Deoxycytidine, Drug Screening Assays, Antitumor, Fluorouracil, Humans, Pancreatic Neoplasms, Spheroids, Cellular, Cell Culture Techniques, Cell Line, Tumor
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