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-kappaB) 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-kappaB 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 microM 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.