Application of Biphasic Numerical Model for the Prediction of Colorectal Carcinoma Cell Response to Co-Treatments

ABSTRACTBackground and Objective: The aim of present study was to apply biphasic numerical model to explain and predict the behaviour of two colorectal carcinoma cell lines in tested co-treatments. Co-treatments consisted as different concentrations Phellinus linteus (methanol extract) with low non-cytotoxic dose cisplatin, or platinum(IV) complexes, or their appropriate ligands, applied simultaneously on SW-480 and HCT-116 cell lines.Methods: Experimental data for cytotoxicity (MTT method) and of cell death type (acridine orange/ethidium bromide staining) were used to estimate parameters of the numerical model. Expression of Frizzle-7 and β-catenin (immunofluorescence) were followed as marker of cell behaviour. Mathematical model was used to obtain parameters related to cell proliferation and cell death and to predict further cellular behavior through determination the efficiency and effectiveness of treatments.Results: Co-treatments induced cytotoxicity after 24 and 72 h, with apoptosis as dominant type of cell death. According to mathematical model parameters the concentration of 25 µg/mL P. linteus+C2 co-treatment can be pointed out as the most efficient concentration on SW-480 cells with the lowest parameter related to proliferation, significant effectiveness and significant impact on the reduction of viability. Additionally, this co-treatment significantly reduced expression of Frizzled-7 and nuclear β-catenin, which confirmed the positive effect of this co-treatment on SW-480 cells. Tested treatments are not recommended for application on the HCT-116 cell due to the sustained viability of rapidly proliferating cells and additional de-differentiation through increased protein expression of the Frizzled-7 receptor.Conclusions: Based on the results of the model, the experimental results can be mathematically confirmed. Additionally, the data for the most effective treatment was obtained. The most efficient concentration does not provoke the cell to a quick response and adaptation, so it can be taken as ideal for re-treatment.