الفهرس 
Statins and its HistoryOnly 14 pages are availabe for public view
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Abstract
The present study was conducted to investigate the effect
of γ-radiation alone and/or combined with cytotoxic drug (Simvastatin) on the viability and the
life cycle of myeloma cells. In preliminary study, Seventeen groups were designed to select three
doses of γ-radiation from eight doses and one dose of Simvastatin from six doses in addition to
three control groups. The P3NS1 myeloma cells were treated with simvastatin (0.1μM/l) 24hr prior to
γ-radiation at doses (0.25,
0.5 and 1Gy). The cell viability, induction of apoptosis and cell death were estimated as well as
generation of ROS, the expression of P53, Bax, Bcl-2, Caspase-3, PARP-1 and Fas genes were
measured. The results indicated that the dose of Simvastatin (0.1μM/l) given 24hr prior to γ-
irradiation (0.5Gy) elevated the percentage of cell death to 37.5% as compared to 4.81% in case of
radiation alone. It was found that, simvastatin treatment before irradiation caused arresting the
cells at G0/G1 and G2/M Phases as assessed by cell cycle analysis using flowcytometry. It is
interesting to find that simvastatin treatment of P3NS1 cells induced an increase in the
intracellular ROS production leading to decreasing the antioxidant enzymes activity with increasing
the expression of P53, Bax and Caspase-3 gene except in case of the Bcl-2 gene
where it was decreased. Consequently, the present results
indicated that pre-treatment of myeloma cells with Simvastatin promote the radiosensitivity of
tumor cells in addition to its apoptotic effect on myeloma cells through intrinsic mitochondrial
pathway. The combination of simvastatin with radiation may induce better results.