LENALIDOMIDE is an immunomodulatory drug that has antiangiogenic, and anti-inflammatory properties. It has shown an efficient anti-myeloma activity. Dexamethasone is a corticosteroid used to treat multiple myeloma (MM). This study aims to evaluate in-vitro and in-vivo the proliferation of myeloma cells after treatment with Lenalidomide, Dexamethasone, γ- irradiation and their combination. In-vitro studies: the treatment effect on the growth of myeloma cells with each of Lenalidomide (0.5-10 μM/ml) or Dexamethasone (10-100 nM/ml) or γ-irradiation (0.5-10 Gy), double combination of the two drugs (Lenalidomide + Dexamethasone) with different doses and triple combination of the two drugs with γ-irradiation doses (0.5-8 Gy) were carried out during 6 days. In-vivo studies: mice bearing ascites were treated with each of Lenalidomide, Dexamethasone or γ-irradiation, double combination of the two drugs and triple combination of the two drugs with γ-irradiation for 3 weeks. Different biochemical parameters were estimated before and after treatment to evaluate the antitumor activities such as β2-microglobulin, cell cycle analysis (flow cytometry), and caspase enzymes.
In-vitro, treatment of myeloma cells with the triple combination (3 μM/ml Lenalidomide +40 nM/ml Dexamethasone + 3 Gy γ-irradiation) has inhibited the growth of myeloma cells within 4 days.
In-vivo, in mice bearing ascites, the triple combination inhibited the growth and decreased the viability % of tumor cells to zero% within 2 weeks. The results obtained from the study of the effective doses showed a reduction in the concentrations of β2-Microglobulins and activation of the levels of caspase 8 and caspase 9 causing a control of the cell cycle.
Treatment of myeloma cells with dual therapy (Lenalidomide-Dexamethasone as a chemotherapy with γ-irradiation as a radiotherapy) resulted in a synergistic effect for treatment of multiple myeloma. This effect increases the growth inhibition, apoptosis, and regression of tumors compared to either treatment agent alone.