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

机译:前列腺癌细胞抗辐射分子基础的实验和系统生物学研究

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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 H2O2. By raising the initial presence of MnSOD in the 0.7–10 μM concentration range, the time-dependent concentrations of H2O2 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 H2O2-mediated elevation of MnSOD expression.
机译:人类前列腺癌细胞PC-3的伽玛电离辐射(IR)抗性的分子机制尚不清楚。由于低LET-IR效应主要通过活性氧(ROS)的产生来体现,因此IR诱导的ROS代谢抗氧化剂(例如Mn和CuZn超氧化物歧化酶(SOD)和过氧化氢酶)的表达),并探讨了转录核因子-κB(NF-κB)。相对于0和2 Gy辐照的细胞,观察到10和20 Gy辐照的细胞中SOD的浓度显着增加,而发现Cat和NF-κB表达相当稳定。建立了系统生物学模型,以阐明MnSOD如何根据H 2 O 2 的产生影响细胞的生物学状态。通过在0.7-10μM的浓度范围内增加MnSOD的初始存在,对比​​了各种初始MnSOD水平下H 2 O 2 的时间依赖性浓度。提示PC-3细胞的放射抗性与H 2 O 2 介导的MnSOD表达升高之间建立的正向,前馈恶性循环有关。

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