Pharmacodynamics modeling based on in vitro 3D cell culture experiments

Abstract

Optimized therapies for the individual patient provide a more cost-effective, more secure method of chemotherapy. Therapy optimization demands a reliable mathematical model of tumor growth, pharmacodynamics, and the effect of the chemotherapeutic agent used during the therapy. Examining these effects and processes in vitro cell culture experiments maintain a cheaper and more ethical method to create tumor growth and pharmacodynamics models and estimate their parameters. In this work, parameter identification was carried out by using cytotoxicity measurements of two- and three-dimensional (spheroid) tumor cell cultures. In vitro experiments were accomplished on mice breast cancer cell line. Four experiments were done: two experiments on two-dimensional cell cultures, with the initial number of 5000 and 10000 cells, and two experiments on three-dimensional spheroid cell cultures, with the initial number of 5000 and 10000 cells. The drug used was Doxorubicin at the same serial dilution in all cases. Parameter identification was performed by fitting to fluorescent intensity confluence data measured by an automatic time-lapse microscope for five days. We compared the results of two- and three-dimensional cell cultures and identified the model parameters in all four cases. The value of the sum square error showed that the fitting and identification performed better in the case of tumor spheroid cultures.