Na <sub> 2 </ Sub> Of Seo <sub> 3 </ Sub> Change And Its Mechanism Of Cell Cycle Induced By Acute Promyelocytic Leukemia Nb4 Cells

Sodium selenite at certain concentrations could inhibit the growth of human APL (acute promyelocytic leukemia)-derived NB4 cells, and induce typical cell apoptosis. Cell growth and proliferation are the result of cell cycle progression, which is under tight regulation by the cell cycle machinery. Thus, the inhibitory effect of sodium selenite on the growth of NB4 cells must have involved the dysregulation of cell cycle progression. Elucidating the effect of sodium selenite on the cell cycle progression of NB4 cells and the relevant pathway, will potently add insight into the mechanism of sodium selenite-induced NB4 cell growth inhibition and apoptosis, thus providing new basis for probing the rationality of treating leukemia.In this thesis, the dose- and time-dependent inhibitory effect of sodium selenite on the growth and proliferation of NB4 cells was confirmed. It was also shown that sodium selenite at certain concentrations or treatment for certain time lengths could significantly change the cell cycle distribution profile of NB4 cells. Further experiments with synchronized cells demonstrated that cells synchronized at G1/S phase and S phase showed significant S phase blockage after sodium selenite treatment, and that the onset of cell cycle profile changes happened much earlier than asynchronized cells. It was also discovered that among asynchronized NB4 cells, DNA replication activities were slightly promoted immediately after sodium selenite treatment (within 6 hrs), while above a treatment time of 12 hrs, DNA synthesizing activities of cells began to display strong inhibitory effects, with a significant proportion of S phase cells ceasing to replicate DNA, and cell cycle progression was blocked at S phase. Besides, synchronized NB4 cells exhibited sodium selenite-induced apoptosis much faster than asynchronized cells, and cells synchronized at S phase were shown to be the most sensitive to sodium selenite-induced apoptosis.Western blot analysis was adopted to analyze the influence of sodium selenite on the levels of several crucial cell cycle proteins, namely cyclin D3, CDK4, cyclin E, CDK2, cyclin A, CDK1, p15, and p27. It was discovered that the level and nuclear localization of these proteins were affected by sodium selenite treatment to different extents. Combined with data from immunoprecipitation studies, these results probably meant that the activities of these cell cycle proteins were among the targets of sodium selenite...