Silencing of GDF15 gene and response to radiotherapy and Temozolomide treatment of glioblastoma multiforme cell lines

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumors in adults beeing less frequent in children, accounting for 7-9% of CNS tumors. Despite technological advances the survival of adult patients is 12 to 15 months. Although a better prognosis compared to adults, a study data showed that in most cases of child GBM, the recurrence and death occurs within two years. Such displays high heterogeneity of tumor cell with complex genetic alterations, reflecting in high genomic instability and present relentless malignant progression, characterized by invasion and spread throughout the brain, resistance to traditional treatments such as radiation therapy and treatment with the drug Temozolomide. Among the genetic changes, our group observed a high GDF15 expression in primary tumors and cell lines of GBM. The GDF15 is a growth factor that in normal physiological conditions is poorly expressed, but in cases of inflammations and malignancies its expression is increased. The high level of GDF15 is associated with poor prognosis in several types of cancers, including GBM. It was observed that the silencing GDF15 resulted in nasopharyngeal tumor cell lines less resistant to radiotherapy. This project aims to correlate the silencing of GDF15 with sensitivity to radiation and treatment with the drug Temozolomide in child and adult cell lines of GBM . To examine these correlations, the GDF15 will be silenced by RNA interference, after the silencing it will be made independent treatments (radiotherapy and Temozolomide) followed by functional in vitro studies.