الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The current study was investigated the anticancer effect of Epigallocatechin-3-gallate (EGCG), Simvastatin, and Gamma radiation individually on myeloma cell line and Ehrlich carcinoma cells (in vitro), in addition to their effect on the solid tumor of the right thigh of mice (in vivo). In the preliminary study on myeloma cells, seven groups were conducted to test and select the dose of EGCG which kill around 50% of cells and then designed nine groups to study the EGCG and its effect in combination with simvastatin (Dual therapy) and\or gamma radiation or both (Triple therapy). Regarding preliminary study on Ehrlich carcinoma cells, twenty groups were conducted to study the different doses of each of EGCG (five doses), Simvastatin (five doses) and Gamma radiation (six doses) and select the dose for each treatment to continue our study. For more confirmation about the potency of those regimens, the solid tumor was induced by intramuscular injection of EC cells in the right thigh of the targeted mice. Magnetic resonance imaging device 1.5 Tesla used for radiology imaging of the normal and ascites-bearing mice under anesthesia. The animals with solid tumors were followed up daily for recording deaths, tumor size, rate of inflammation, and gangrene in the tumor area of the hind limb. Magnetic resonance imaging showed the intraperitoneal ascites and the soft organs (liver, kidney, and intestine), which were bright in the case of the ascites-bearing mouse than the normal control. The doses of Simvastatin, EGCG and Gamma radiation induced cytotoxicity about 50% of cells on myeloma cells and Ehrlich carcinoma cells as the follows: (0.1µmol/L and 0.5µmol/L), (50µmol/L and 100µmol/L) and (1Gy and 4Gy), respectively. Cell cycle arrest was detected: Gamma radiation induced S phase and G2/M arrest, Simvastatin induced G0/G1 and G2/M arrest, EGCG induced G0/G1 arrest and combination therapies with Simvastatin induced G2/M checkpoint arrest. More investigation was evaluated for more clarifying the mechanism of action, and in general, the effect of current regimens induced oxidative stress and downregulated the activity of antioxidant enzymes in addition to upregulation of apoptotic genes (BAX, CASPASE-3, and FAS genes), downregulation of the anti-apoptotic gene (Bcl2), upregulation of PARP gene which is the first detector of DNA damage and finally upregulation of tumor suppressor gene (P53). In vivo study on solid tumors, the triple therapy regimen significantly reduced the tumor size (662.6±12.5) compared to the positive control (825±21.8 mm3). It increased the survival rate to 66.7% compared to 25% in the positive control. Triple therapy reduced the inflammation of tumor area, preventing the gangrene incidence of the lower limb, and showed the best value of T/C=142, ILS%=42.11 and TIR %=19.6 compared to the positive control and single treatments. Consequently, the present results confirm the efficacy of each EGCG and Simvastatin as anticancer in addition to confirming the synergism between EGCG, Simvastatin, and Gamma radiation on killing cancer cells in vitro, decreasing the tumor size and increasing the survival rate of tumor-bearing mice from 25% to 66.7%. So it is considered as an anti-tumor regimen according to the national cancer institute criteria.