Platform based on mist spheroid as a tool for prediction of antitumor potential on colorretal cancer cells

Abstract

Colorectal cancer is still top 3 in the cause of cancer death worldwide. The late diagnosis together with the resistance acquisition of this cancer, are responsible for the low efficiency of the therapeutic protocols available. Thus, more effective therapeutic strategies are desirable. To this end, the molecular knowledge of cancer biology and the use of cellular models with a complexity level closer to that found in vivo becomes crucial. In this context, different in vitro 3D models have been developed, in recent years, to simulate the tumor microenvironment and serve as important tools to better understand/predict tumor characteristics in vivo, such as hypoxia, desmoplasia, dormancy, drug penetration, toxicity and therapeutic resistance. Therefore, our research group has invested in the standardization and validation of the 3D culture of different cancers, including colorectal cancer. Thus, the present project aims to develop mist spheroids (mini-tumors) and to characterize them from the metabolic point of view (glycolytic and oxidative metabolism). To this end, colorectal HT29 cell line (glycolytic phenotype - Warburg effect predominant) and HCT116 (oxidative phenotype) will be used. In addition, the ability of mitoxantrone to decrease the viability of these mini tumors will be investigated. Therefore, we aim with this project, not only to technically qualify the student, but to identify metabolic characteristics of the 3D tumor that may predict the responsiveness of tumors to the death stimulus. In this aspect, we do believe that the focus on glucose metabolism is relevant, once in general, more glycolytic tumors have greater resistance. In addition, we consider that the platform (mist 3D) will allow large scale analysis of biomolecules with potential antitumor action.