摘要
The present study investigated the nuclear transportation phenomenon of ^125I-nerve growth factor （NGF） and the DNA-damaging changes to U251 cells using microautoradiography and single cell electrophoresis. The results showed that ^125I-NGF inhibited the survival of p53 mutant U251 human glioma cell/tumor and enhanced the therapeutic effectiveness of vincristine in in vivo and in vitro models. In vitro experiments showed ^125I-NGF was transported into the nucleus and damaged the DNA in U251 cells. Moreover, ^125I-NGF locked the U251 cells in the G2 phase. Further investigation showed that ^125I-NGF decreased cyclin B1 protein levels in a dose dependent manner, but the level of cyclin B1 mRNA expression remained unchanged. ^125I-NGF increased phosphorylated Chkl, Chk2 and Cdc25c protein levels in U251 cells, but did not influence p53 and p21 protein expression. Moreover, ^125I-NGF and vincristine exhibited synergistic effects on reducing cyclin B1 protein levels. These results indicate that ^125I-NGF can provide anti-tumor effects by activating the ATM and ATR pathways through DNA damage.
The present study investigated the nuclear transportation phenomenon of ^125I-nerve growth factor （NGF） and the DNA-damaging changes to U251 cells using microautoradiography and single cell electrophoresis. The results showed that ^125I-NGF inhibited the survival of p53 mutant U251 human glioma cell/tumor and enhanced the therapeutic effectiveness of vincristine in in vivo and in vitro models. In vitro experiments showed ^125I-NGF was transported into the nucleus and damaged the DNA in U251 cells. Moreover, ^125I-NGF locked the U251 cells in the G2 phase. Further investigation showed that ^125I-NGF decreased cyclin B1 protein levels in a dose dependent manner, but the level of cyclin B1 mRNA expression remained unchanged. ^125I-NGF increased phosphorylated Chkl, Chk2 and Cdc25c protein levels in U251 cells, but did not influence p53 and p21 protein expression. Moreover, ^125I-NGF and vincristine exhibited synergistic effects on reducing cyclin B1 protein levels. These results indicate that ^125I-NGF can provide anti-tumor effects by activating the ATM and ATR pathways through DNA damage.
基金
the National Natural Science Foundation of China, No. 30701031
the National Basic Research Program of China (973 Program), No. 2009CB521807
Senior Expert Fund of Jiangsu University, No. 06jdg045
