Pharmacophore an International Research Journal
Glioblastoma multiforma (GBM), the most malignant brain cancer, is currently treated with surgery followed by radiotherapy and concurrent chemotherapy. In spite of much efforts made to improve the treatment, outcome is still unsatisfactory. Lomustine is an alkylating agent which is used for GBM treatment. Combination of different doses of lomustine with radiation may result in different cytotoxicity against cancer cells. Optimization of radiation dose and lomustine concentration to generate synergy can help to resolve some problems with GBM treatment. In this study, in order to examine the combination effect on U87-MG cancer cells concentrations of 25, 50 and 100 ug/ml lomustine were used in combination with doses of 1, 2, 4 and 6 Gy 6 MV X rays’ radiation. MTT was performed to evaluate the cytotoxicity of either lomustine or radiation separately as well as in combination. For examination of survival fraction of U87-MG cells treated with lomustine and irradiated to radiation colony assay was performed. Combination index calculations were used for investigation of combination effect. Results showed that U87-MG cells viability decreased by increasing lomustine concentration and radiation dose (p< 0.05). For combination of 1 Gy radiation dose with lomustine at concentrations of 25, 50 and 100 ug/ml CI was close to 1 representing additive effect and for other situations, the effect was antagonism (CI < 1). It is promising for patients with GBM to be treated by radiotherapy and concurrent chemotherapy if possible to increase lomustine uptake by cancer cells to the above levels through targeted drug delivery or by other mechanisms.
