Introduction: Glioblastoma multiforme (GBM) is a stage IV aggressive brain cancer, which has poor prognosis with a median survival of 12-15 months. Conventional treatment approaches consisting of surgical resection and chemo- and radiotherapy offer only pallia-tion expanding the lifetime by a few months. The inevitable regrowth of GBM is thought to be caused by a subpopulation of glioblastoma-initiating cells (GICs), which is characterized by their special migratory properties, stem cell characteristics, and resistance to conven-tional therapies. The protein Cripto-1 (CR-1) has been correlated to the pathogenesis of cancer and identified as a possible marker for GICs, which can be an attractive target for cancer therapy.
Methods: GBM cell lines U87, T78, and T87 were exposed to a double-cycle treatment with cytostatic temozolomide (TMZ). DMSO-treated cells were used as the vehicle control group. The effect of the TMZ-treatment on GBM cell lines was investigated using function-al assays regarding cell viability and proliferation as well as self-renewal ability. Further-more, the effect of TMZ-treatment on CR-1 expression and its relation to the self-renewal ability of GICs was explored using qPCR and flow cytometric analysis.
Results: U87 cells demonstrated sensitivity to the treatment in regards to viability, prolif-eration, and self-renewal ability. CR-1 expression showed to decrease upon TMZ-treatment. T78 cells showed a decrease in functional features upon first treatment cycle, where a revival was observed upon second cycle. T87 demonstrated similar features as the control DMSO group while an increase in CR-1 expression was displayed upon second TMZ treatment cycle. DMSO-treatment showed to decrease the cellular proliferation for all three cell lines.
Conclusion: The GBM cell lines responded differently to the TMZ double-cycle treat-ment, which may be related to their genetic tumor profiles. The features of GICs have not been possible to detect in this study by using CR-1 as a possible marker for GIC population. Further research is therefore needed in order to investigate the effect of TMZ on GBM in vitro models and how the GIC population is affected by therapeutic selection pressure by TMZ.