Prediction and validation of avascular tumor growth pattern in different metabolic conditions using in silico and in vitro models

Abstract

Objectives: In recent years, scientists have taken many efforts for in vitro and in silico modeling of cancerous tumors. In fact, three-dimensional (3D) cultures of multicellular tumor spheroids (MCTSs) are good validators for computational results. The goal of this study is to simulate the 3D early growth of avascular tumors using MCTSs and to compare the in vitro models with the results and predictions of a specific computational modeling framework. Using these two types of models, the importance of metabolic condition on tumor growth behavior and necrosis could be predicted. Materials and methods: We took advantage of a previously developed computational model of tumor growth (constructed by integrating a generic metabolic network model of cancer cells with a multiscale agent-based framework). Among the computational predictions is the importance of glucose accessibility on tumor growth behavior. To study the effect of glucose concentration experimentally, MCTSs were grown in high and low glucose culture media. After that, tumor growth pattern was analyzed by MTT assay, cell counting and propidium iodide (PI) staining. Results: We obviously observed that the rate of necrosis increases and the rate of tumor growth and cell activity decreases as the glucose availability reduces, which is in line with the computational model prediction.