To investigate the effect of genistein on ultrastructure and the intranuclera localization of tumor suppressor gene PTEN in NSCLC A549/DDP cell.Method: The cultured human non-small cell lung cancer A549/DDP cells were divided into different groups administrated with different concentrations of genistein including control group,40μg/ml,60μg/ml,and 80μg/ml,and also the specific inhibitor of PI3K group(for 48h).The transmission electron microscope was used to detect the alteration of the ultrastructural of cells from different experimental groups.The content of IP3 in cell was analyzed by the ELISA assay.The PTEN staining showing nuclear localization was observed by the laser confocal microscope.Result: 1).Through the observation on the transmission electron microscopy(tem),we found that compared with the control group mitochondria and endoplasmic reticula in A549/DDPcells treated with genistein had varying degrees of swelling or even vacuolation,a vesicle sample change happend in it and the mitochondrial crest fracture occurred.Some mitochondria cristae showed broken with higher does of genistein or longer treatment time,apoptosis and necrosis were observed in cell.2).Detection of intracellular IP3 by ELISA: with the increased does and longer exposure of genistein,the intracellular IP3 concentration was gradually reduced compared with the control group.3).When A549/DDP cells were treated with genistein and LY294002,respectively.observed under confocal microscopy,we found that endogenous PTEN was translocated from cytoplasm to nucleus.Conclusion: The data presented here reveals that genistein could induce the alteration of mitochondria and endoplasmic reticulum,results in apoptosis of A549/DDP cells,and in the meanwhile,it could also reduce the content of IP3 signal molecules and urge PTEN protein translocation from cytoplasm to nucleus.