title: The effect of primary cancer cell culture models on the results of drug chemosensitivity assays: the application of perfusion microbioreactor system as cell culture vessel.
abstract: To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture condition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was adopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity assay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that minor environmental pH change could significantly affect the metabolic activity of cells, demonstrating the importance of stable culture condition for such assays. Moreover, the culture models could also significantly influence the metabolic activity and proliferation of cells. Furthermore, the choice of culture models might lead to different outcomes of chemosensitivity assays. Compared with the similar test based on tumor-level assays, the spheroid model could overestimate the drug resistance of cells to cisplatin, whereas the 2D and 3D culture models might overestimate the chemosensitivity of cells to such anticancer drug. In this study, the 3D culture models with same cell density as that in tumor samples showed comparable chemosensitivity assay results as the tumor-level assays. Overall, this study has provided some fundamental information for establishing a precise and faithful drug chemosensitivity assay.
authors: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan ; Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan.
authors: Chia-Hsun
authors: 0000-0002-5547-409X
authors: CH
authors: Hsieh
authors: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan.
authors: Yi-Dao
authors: YD
authors: Chen
authors: Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan.
authors: Shiang-Fu
authors: SF
authors: Huang
authors: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan.
authors: Hung-Ming
authors: HM
authors: Wang
authors: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan.
authors: Min-Hsien
authors: 0000-0002-3507-3512
authors: MH
authors: Wu
mesh_terms: D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009055:Mouth / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology; D010477:Perfusion; D014407:Tumor Cells, Cultured
chemical_list: D002945:Cisplatin
references: Chemotherapy. 2001 Mar-Apr;47(2):136-42
references: 11173816
references: Oncol Rep. 2014 Aug;32(2):641-9
references: 24927163
references: Nature. 2003 Aug 21;424(6951):870-2
references: 12931155
references: Biochem Pharmacol. 1990 Nov 15;40(10):2353-62
references: 2244936
references: Med Pediatr Oncol. 1994;23(2):124-9
references: 8202034
references: Nat Rev Cancer. 2004 Nov;4(11):891-9
references: 15516961
references: J Natl Cancer Inst. 2005 Nov 16;97(22):1663-70
references: 16288119
references: Nat Rev Mol Cell Biol. 2006 Mar;7(3):211-24
references: 16496023
references: Nature. 2006 Jul 27;442(7101):403-11
references: 16871208
references: Cancer Res. 2006 Sep 15;66(18):8927-30
references: 16982728
references: Biomed Microdevices. 2006 Dec;8(4):331-40
references: 16917663
references: Biomed Microdevices. 2007 Feb;9(1):25-34
references: 17103048
references: Biotechnol Prog. 2007 Mar-Apr;23(2):430-4
references: 17286385
references: Nat Rev Mol Cell Biol. 2007 Oct;8(10):839-45
references: 17684528
references: Biotechnol Bioeng. 2008 Mar 1;99(4):986-95
references: 17929321
references: Clin Exp Med. 2009 Mar;9(1):1-7
references: 18818983
references: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):40-5
references: 20018687
references: Arch Pharm Res. 2009 Dec;32(12):1737-42
references: 20162402
references: Biomed Microdevices. 2010 Jun;12(3):389-98
references: 20107907
references: Tissue Eng Part B Rev. 2010 Jun;16(3):351-9
references: 20092396
references: Biomaterials. 2010 Nov;31(32):8494-506
references: 20709389
references: Analyst. 2011 Feb 7;136(3):473-8
references: 20967331
references: Biomed Microdevices. 2011 Feb;13(1):131-41
references: 20957436
references: Int J Cancer. 2011 May 1;128(9):2038-49
references: 20648559
references: Acta Pharmacol Sin. 2012 Mar;33(3):401-6
references: 22286916
references: J Control Release. 2012 Dec 10;164(2):192-204
references: 22613880
references: PLoS One. 2012;7(12):e51754
references: 23300565
references: Lab Chip. 2013 Mar 21;13(6):1133-43
references: 23353927
references: Acta Oncol. 2014 Feb;53(2):242-50
references: 23713890
references: Cancer Res. 2014 Mar 1;74(5):1554-65
references: 24436149
references: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1484-9
references: 12552122