In vitro monitoring of cellular respiration of different tumor cell lines and the effect of drugs and metabolites.

Studying tumor metabolism and how cells exploit the resources around them could provide important clues regarding the therapy which[HB5.1] can be used to counteract it, directing the choice toward one drug rather than another or one procedure rather than another. This thesis investigates how mitochondrial metabolism, particularly O2 consumption, can modify cell growth and development. O2 utilization is controlled as far as possible by the utilization of substances such as Oligomycin and 2-DG, the increase or decrease of Glucose, Glutamine and Lactic Acid. Oxygen consumption is measured through a commercial assay based on a fluorescent sensor that reveals the O2 concentration inversely within previously cultured tumor cell plates. Another fundamental step that would increase awareness in therapy could be predicting what is happening in the cell, always at the metabolic level, and for this reason the creation of a mathematical model can be an important support for this purpose. The model construction in this thesis is addressed with Matlab, a fundamental software for translating the language of metabolism into statistical, predictive, and interpretable mathematical language so that it can be applied and adapted. The construction of the model follows the main steps of cellular metabolism in a simplified way, not only in order to be able to adapt it to all cell types, even those different from those used in this thesis, but also because a more complex model including the enzymatic equilibrium constants would have required more time and instrumentation than those available for this project. The versatility was exploited as a strength for possible use for other cells. The in vitro study of metabolism and model building could be a valuable combination in the fight against tumor.