摘要
【目的】探讨MDM2基因在不同应激状态下对T细胞性白血病细胞株Jurkat增殖、凋亡和基因表达的影响。【方法】采用RNA干扰下调白血病细胞株JurkatMDM2基因表达后,用Westernblot、流式细胞术等方法检测Jurkat细胞在不同应激状态下的变化。【结果】无应激状态下,MDM2基因表达下降后,Jurkat细胞增殖减慢,细胞周期表现一定程度的G1-S阻滞;E2F1表达明显降低超过78%,p65表达下调超过58%;细胞损伤后,MDM2表达下调可导致细胞损伤修复减慢,增强紫外线和甲氨喋呤诱导凋亡作用,导致甲氨喋呤作用下Rb和Bax基因的表达相对增加。【结论】在不同应激状态下,MDM2基因表达下降广泛影响Jurkat细胞的增殖、凋亡和基因表达等生物学特性,提示MDM2基因有可能作为T细胞性白血病治疗的潜在新靶点。
[ Objective ] To investigate the effect of MDM2 gene on the proliferation, apoptosis, and gene expression of T-cell leukemia Jurkat ceils under different stress states. [Methods] After knockdown of MDM2 gene by RNAi, the modification of T lymphoblastic leukemia Jurkat cells under different stress states was assessed by Western blot analysis and flow cytometry. [ Resuhs]Mter down regulation of MDM2 gene under no stress reaction, the growth of Jurkat ceils was slow and the certain extent of G1-S arrest was observed. On the other hand, the expression of E2F1 and p65 protein was obviously down-regulated by 78% and 58%, respectively. When the ceils were injured, the knockdown of MDM2 gene slowed the process of repairrnent and increased the apoptosis of UV irradiation and induced by methotrexate. Consquently, the expression of Rb and Bax was upregulated with the effects of MTX. [Conclusion] The present study showed that the knockdown of MDM2 may have broad effects on the biological characteristics of Jurkat cells such as proliferation, apoptosis, and gene expression under different stress states. The results suggested that MDM2 gene may be the new target for treatment of T-cell leukemia.
出处
《中山大学学报(医学科学版)》
CAS
CSCD
北大核心
2005年第5期545-548,共4页
Journal of Sun Yat-Sen University:Medical Sciences