Synergistic Effect of some Chemotherapeutic Drugs with Gamma Radiation on the Proliferation of Myeloma Cells | ||||
| Egyptian Journal of Radiation Sciences and Applications | ||||
| Article 3, Volume 33, Issue 2, December 2020, Page 89-100 PDF (1.21 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejrsa.2020.44876.1104 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Hanan M. Elshershaby  1; Nahed Ebied1; Kamel Abd el hameed1; Nasr Allahloubi2
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| 1Labeled Compounds Department, Hot Laboratories Center, Atomic Energy Authority, Egypt | ||||
| 2National Cancer Institute, Cairo, Egypt | ||||
| Abstract | ||||
| 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. | ||||
| Keywords | ||||
| Dexamethasone; Lenalidomide; Myeloma; γ-irradiation | ||||
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