3.5. Validation of αCT1-temozolomide treatment in patient-derived glioblastoma organoids
It has been established that studies using cell lines are limited (Fusenig et al., 2017). Cell lines often consist of a homogeneous population of cells that only represents a subset of the cells found in the heterogenous tumor in the patient. It has also been confirmed that some cell lines, namely the U87 cell line, are genetically and phenotypically different from the original cells obtained from patients many years ago (Allen et al., 2016). To partially address this issue, we used the BT169 cell line which is not immortalized and is cultured in conditions that enhance the formation of a heterogeneous population. Even so, we sought to validate that the combinatorial treatment of αCT1 and TMZ is effective in a patient derived GBM cell population.
The highest concentration of TMZ (1000 μM) killed most of the cells in our patient-derived cell population even without αCT1 (Figure 6 ). However, TMZ only was ineffective at lower concentrations (10 μM and 100 μM). Combinatorial treatment with αCT1 and TMZ resulted in significant decreases in cell viability in the TMZ 100 μM group. Interestingly, there was also a significant decrease of viability in the αCT1=100 μM, TMZ=0 condition, again indicating that αCT1 also induces other cellular changes in some subsets of GBM cells.