PP49. assessment of apoptosis induced by metformin in GBM in vitro.
Abstract
The development of new treatments for glioblastoma multiforme (GBM) is time-consuming and expensive and hence, the repurposing of existing medication could expedite new treatment strategies. Metformin is currently the most common antidiabetic drug treatment for type 2 diabetes in the world. Recent studies have demonstrated anti-proliferative effects of metformin in vitro in a range of tumour types. Although the mechanisms by which metformin exerts its anti-tumour effects are not fully understood, in prostate, pancreatic and lung cancer metformin has been shown to induce apoptosis. Previously, the ID50 values of a panel of 13 patient-derived GBM short-term cultures and the U251MG cell line to metformin were determined. Response to metformin has been shown to be significantly linked to p53 status. Induction of apoptosis following treatment with an ID50 dose of metformin was determined in 5 GBM short-term cultures and U251MG (ID50 values range from 1.45 to 25.34mM) and NHA (ID50 75mM) using flow cytometry. This was carried out at 24, 48, 72 and 96 hours post-treatment with metformin in media containing 3mM or 6mM glucose. The activity of caspases 3 and 7 in these cultures was also assessed at 72 and 96 hours post-treatment with metformin. In all cultures, the response to metformin was evident towards the end of the time course, with changes in cell populations only becoming apparent after 72 hours of treatment. Reduction of glucose in treatment media caused a significant (p=…
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