摘要
目的通过研究在人急性髓性白血病(AML)中NB4和耐药细胞株NB4/ADR的唾液酸糖基转移酶ST8SIA4的表达差异,探讨ST8SIA4基因的差异表达在AML细胞体内外药敏性的影响,为AML多药耐药的检测提供新的标志物,同时为逆转其耐药提供新策略和靶点。方法采用Real-time PCR、Western blot技术检测人AML细胞株ST8SIA4的表达情况。通过对ST8SIA4特异性调控,检测NB4/ADR细胞在体内和体外干扰前后对化疗药物的敏感性变化、信号通路PI3K/Akt的激活情况和P-gp的表达情况。结果在人AML和耐药细胞株中ST8SIA4的表达具有明显差异;特异性下调ST8SIA4在NB4/ADR细胞中的表达,药敏性在该细胞中增强;PI3K/Akt信号通路主要分子p110α、p-Akt308、p-Akt473在NB4/ADR-ST8SIA4sh RNA细胞中表达较少,同时P-gp的表达量减少。结论 ST8SIA4在人AML和耐药细胞株中表达具有明显的差异,AML多药耐药与ST8SIA4的特征性改变具有相关性;AML的多药耐药性可能是通过介导ST8SIA4的信号通路PI3K/Akt来调控P-gp表达改变的。
Objective To study the differential expression of sialyltransferase ST8SIA4 in acute myeloid leukemia（ AML） NB4 and drug-resistant cell lines NB4 /ADR,clarify the effect of ST8SA4 on the drug sensitivity of leukemia cells in vitro and in vivo,predict and diagnose the multidrug resistance of AML,and provide a new therapeutic strategy and target point in AML. Methods The expression of ST8SIA4 in AML cell lines was detected by Realtime PCR and Western blot. By manipulating the differentially expressed ST8SA4 genes,the chemosensitivity of NB4 / ADR to anti-tumor drugs in vitro and in vivo was detected. The activity of PI3 K / Akt signaling pathway and the expression of P-gp were also detected. Results ST8SIA4 was differentially expressed in AML cells and drugresistant cell lines. Inhibition of ST8SIA4 expression resulted in increased drug sensitivity,decreased expression of the main molecules p110α,p-Akt308 and p-Akt473 of PI3 K / Akt signaling pathway and the expression of P-glycoprotein（ P-gp） in NB4 / ADR-ST8SIA4 sh RNA. Conclusion ST8SIA4 are differentially expressed in AML cells and drug-resistant cell lines. These characteristic alterations of ST8SIA4 are associated with multidrug resistance of AML. The multidrug resistance of AML is probably changed through ST8SIA4 regulating the activity of PI3 K / Akt signaling and the expression of P-gp.
出处
《中国微生态学杂志》
CAS
CSCD
2015年第7期761-765,共5页
Chinese Journal of Microecology
基金
国家自然科学基金(81271910)
