PO-283 The Akt/mTOR pathway in cancer stem/progenitor cells is a therapeutic target for glioblastoma and neuroblastoma

Introduction Many studies are focusing on the pathogenic role of the Akt pathway and the mechanistic target of Rapamycin (mTOR) complex in mediating the progression of various types of cancer, including highly aggressive nervous system tumours such as neuroblastoma and glioblastoma, in order to develop efficient targeted therapies. Other studies are also elucidating the mechanism of cancer stem cells (CSCs), a small population of treatment-resistant cancer cells, in replenishing tumours and are devising novel treatments to prevent recurrence in various cancer subtypes. Material and methods In our study, the effects of Triciribine (p-AKT inhibitor) and Rapamycin (mTOR inhibitor) were assessed in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) cell lines. First, through validating pathway inhibition by both drugs via Western blot analysis of protein expression; second, by observing the in vitro effect of both drugs on the cell proliferation of U251 and SH-SY5Y, via MTT assays; third, by assessing the inhibitory effect of our drugs on migratory and invasive capabilities of the cancer cell lines via wound healing and invasion assays; and fourth, by studying the inhibitory effect of increasing dose concentrations of our drugs on U251 and SH-SY5Y neurospheres. Results and discussions Using Western blot analysis, we proved that Rapamycin and Triciribine specifically inhibit downstream phosphorylation of the mTOR and Akt, respectively. Moreover, Triciribine and Rapamycin minimally decrease the survival of U251 and SH-SY5Y cell lines in a 2D model, while this effect was much more pronounced in a 3D culture model. Furthermore, both drugs significantly decreased the migratory and invasive abilities of these cancer cell lines and decreased the sphere-forming units (SFU) of both cells by extinguishing their CSC population. Conclusion Rapamycin and Triciribine proved to be effective in vitro treatments of glioblastoma and neuroblastoma cell lines, by targeting their CSC population, and inhibiting migration and invasion index.