The purpose of this project is to evaluate the synergistic growth inhibitory effect of the combination of the gold standard gemcitabine (GEM) with cannabinoids in different pancreatic adenocarcinoma cell lines and to study the molecular mechanisms associated, with particular interest to those involved on oxidative stress generation.
In particular, the goals of the project are:
- study of the molecular mechanisms involved in the intracellular oxidative stress induction by GEM or cannabinoids;
- study of the effect of GEM on mitochondria: DNA synthesis, gene expression and activity of the respiratory chain complexes;
- identification and functional evaluation of novel and ROS-associated biomarkers involved in the cellular response to GEM;
- pancreatic tissue validation of the biomarkers identified;
- improvement of GEM sensitivity of low responsive cell lines by adding cannabinoids to GEM, in vitro and in vivo;
- study of the proteomic profile before and after treatment with GEM and/or cannabinoids;
- evaluation of the anti-tumoural properties of GEM and/or cannabinoid treatments on cell lines from a wide panel of tumour types.