Signal pathway in apoptosis of K562 cells induced by STI571 / 中国实验血液学杂志

ABSTRACT

This study was aimed to investigate the effect of tyrosine kinase inhibitor (STI571) on growth and proliferation of K562 cells by using microarray method, the changes of gene expression in the process of K562 cell apoptosis induced by STI571 and the mechanism of K562 cell apoptosis. The gene microarray probes were prepared by RD-PCR technique, then the microarray of gene expression map was constructed; the morphologic changes of K562 cells were observed under phase-contrast microscopy before and after treatment with STI571; the apoptosis of K562 cells treated with STI571 was assayed by MTT method; the expression level of genes was analyzed by self-made microarray. The results indicated that after the treatment of STI571 for 24 hours, in K562 cells appeared major morphological changes, which included nuclear shrinkage, membrane bleb and scattered apoptotic bodies. DNA gel electrophoresis also showed that the typical "DNA ladder" phenomena existed in the treated group. After hybridization, detection and analysis with microarray method, expression of 9 genes significantly down-regulated and expression of 4 genes up-regulated. These differentially expressed genes included cell cycle related genes, cell metabolizing pathway related genes, signal transduction and transcription regulation related genes and antiapoptosis genes. It is concluded that STI571 can effectively inhibit the K562 cell growth and induce K562 cell apoptosis. The genes screened from this microarray offer new information for exploration of pathogenesis of K562 cell malignant transformation and shows abundant potential targets for the treatment of CML.