Evaluating new treatment strategy for medulloblastoma

Purpose: Medulloblastoma is the most common malignant pediatric brain tumor. Although chemotherapy, radiation, and surgical resection are often successful, patients in remission often suffer from long-term side effects and face the potential for re-growth of their cancer. This raises a need for effective, less toxic therapeutic strategies. An anti-apoptotic protein, Survivin, and its transcription factor, Sp1, are over-expressed in most cancers including medulloblastoma and are associated with a poor prognosis. Metformin, an anti-diabetic drug with relatively low toxicity profile, was found to have anti-cancer properties in many cancers. This study was conducted to evaluate the effects that Metformin has on the inhibition of medulloblastoma cells. We hypothesize that Metformin treatment will decrease the growth of medulloblastoma cells, possibly by inhibiting Survivin expression through Sp1 transcription factor downregulation. Methods: Human medulloblastoma cells were treated with increasing Metformin doses, then cell viability was assessed at 24 and 48 hours post-treatment using a CellTiter-Glo cell viability assay. Survivin and Sp1 expression in Metformin-treated cells was assessed by Western blot analysis. Results: As the concentration of Metformin increased, the number of metabolically active cells decreased. Sp1 and Survivin protein levels were reduced by Metformin in a dose/time dependent manner. Conclusion: The results validated that Metformin treatment resulted in reduced cell proliferation and decreased Survivin expression. Given that high Survivin levels are associated with resistance to chemotherapy and radiation, future studies will evaluate whether inhibiting Survivin using Metformin will sensitize cancer cells to chemotherapy.