To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture\ncondition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was\nadopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity\nassay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that minor\nenvironmental pH change could significantly affect the metabolic activity of cells, demonstrating the importance of stable culture\ncondition for such assays. Moreover, the culture models could also significantly influence the metabolic activity and proliferation\nof cells. Furthermore, the choice of culture models might lead to different outcomes of chemosensitivity assays. Compared with the\nsimilar test based on tumor-level assays, the spheroid model could overestimate the drug resistance of cells to cisplatin, whereas the\n2D and 3D culture models might overestimate the chemosensitivity of cells to such anticancer drug. In this study, the 3D culture\nmodels with same cell density as that in tumor samples showed comparable chemosensitivity assay results as the tumor-level assays.\nOverall, this study has provided some fundamental information for establishing a precise and faithful drug chemosensitivity assay.
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