Experimental and Systems Biology Studies of the Molecular Basis for the Radioresistance of Prostate Carcinoma Cells

Molecular mechanisms for the gamma-ionizing radiation (IR) resistance of human prostate cancer cells, PC-3, are not quite clear. Since the low-LET-IR effects are primarily manifested by the generation of reactive oxygen species (ROS), the IR-induced expressions both of ROS-metabolizing antioxidant enzymes, such as Mn- and CuZn superoxide dismutases (SODs) and catalase (Cat), and of the transcriptional nuclear factor-kappaB (NF-κB) were explored. A substantial increase in the concentrations of SODs was observed in the cells irradiated by 10 and 20 Gy relative to those irradiated by 0 and 2 Gy, while the Cat and NF-κB expressions were found to be fairly stable. A system biology model was developed to shed more light on how MnSOD affects the biological state of cells depending upon the production of H 2 O 2 . By raising the initial presence of MnSOD in the 0.7–10 μ M concentration range, the time-dependent concentrations of H 2 O 2 for various initial levels of MnSOD were contrasted. The radioresistance of PC-3 cells is suggested to be associated with the positive, feed-forward vicious circle established between the H 2 O 2 -mediated elevation of MnSOD expression.