The Different Expression Of Survivin Gene In GC-sensitive And GC-resistant Leukemia Cell Line And Its Clinical Significance

Objective Survivin is expressed in almost all human tumor cells and is considered to play an core role in inhibition of apoptosis. Glucocorticoid(GC) is a very important chemtheropy drug throughout the treatment of childhood acute lymphoblastic leukemia (ALL). And GC resistance is a poor prognostic factor in the diagnosis of childhood ALL. The specific mechanism of GC resistance has not yet been clarified. Recent studies reveal that the abnormal apoptosis pathway is a new mechanism of tumor cells resistance. In this study, We compared different survivin gene expression in GC-sensitive(CEM) and GC-resistant(Jurkat) T-cell leukemia lines and aimed to reveal a new mechanism for GC resistance.Methods Simulated GC sensitive and resistant leukemia cells in the newly diagnosed and treatment of childhood ALL, Study were divided into unexposed group and exposed group, And let the negative control and blank control. Dexamethasone sodium phosphate(DEX) inhibit of cell proliferation was assay by MTT. Cell apoptosis was examined by Flow cytometry; Survivin mRNA level was detected by RT-PCR; survivin protein were evaluated through Western Blot.Results The DEX inhibition effect was dose and time dependent, CEM 24h IC50 and 48h IC50 are 13μmol/l, 3μmol/l;Jurkat 24h IC50 and 48h IC50 are 442μmol/l, 273μmol/l. Jurkat cells treated with Dex(100μM, 48h)exhibited typical apoptotic features. In the unexposed group: the level of survivin expression in Jurkat cell was significantly higher than CEM (P<0.05); In the exposed group: With increasing of the GC concentration, survivin expression in CEM cell was significantly decreased (P<0.01); but there were no significant difference in Jurkat cell(P>0.05).Conclusion In the Simulated study: unexposed group, The expression of Survivin gene in GC-resistant leukemia cell line was higher than GC-sensitive leukemia cell line. Its expression level might related to the GC treatment of newly diagnosed childhood ALL. Exposed group, Survivin gene in GC-resistant leukemia cell line was persistent and high express, while in GC-sensitive leukemia cell line was Sharply decreased. Survivin overexpression persisting in GC-resistant ALL cells might be lead to GC resistance. Reversed the survivin gene overexpression might provide a new therapeutic method for the treatment of GC resistance children.