Glioblastoma is an aggressive primary brain tumour with five-year survival rates of less than 10%. These tumours are heterogeneous in nature, though commonly display an overexpression of the epidermal growth factor receptor (EGFR), leading to increased tumour growth, motility and survival. Glioblastomas are considered incurable, as the current therapeutic options are ineffective, and are associated with adverse effects and poor quality of life for patients. Therefore, alternative chemotherapeutic agents and targeted drug delivery mechanisms are required to improve patient outcomes.
This study’s aims include to investigate cytotoxicity of emodins and carbon monoxide releasing molecules (CORMs) on the glioblastoma cell lines T98G and U87MG, and the normal kidney cell line HEK293T; and to investigate the selectivity of EGFR targeting aptamers, to determine efficacy as a potential drug-delivery platform for the treatment of glioblastoma.
The cell lines T98G, U87MG and HEK293T were used to determine therapeutic efficacy of aloe-emodin, emodin, CORM-2 and CORM-3. Cells were treated with either aloe-emodin, emodin, CORM-2 or CORM-3 at increasing concentrations (10µM – 100µM) for 24, 48 and 72 hours. Cell viability was assessed using MTT assays and flow cytometry. Aptamers targeting EGFR were incubated with the cell lines T98G, U87MG and HEK293T to determine aptamer specificity to the cancer cells, and confirmed through flow cytometry and confocal microscopy.
The emodins and CORMs were found to significantly decrease cell viability in all cell lines. The EGFR aptamers bound to the glioblastoma cells, and were successfully internalised. No binding or internalisation were observed in the control cell line, confirming their specificity for glioblastoma cells.
These results indicate that emodins and CORMs are capable of inhibiting cell growth, and therefore have potential to be used as chemotherapeutic agents against glioblastoma. However, as these drugs do not preferentially target glioblastoma cells, they should be used in conjunction with an EGFR aptamer to ensure drug-delivery directly to the tumour; thereby increasing treatment efficacy, sparing healthy tissues and reducing off-target effects associated with chemotherapy.