人质膜型唾液酸酶与人红白血病细胞多药耐药相关

基础医学与临床 ›› 2010, Vol. 30 ›› Issue (2): 139-143.

人质膜型唾液酸酶与人红白血病细胞多药耐药相关

许莉孙连坤李峰禹彬李晓洁赵雪俭李扬

吉林大学白求恩医学院吉林大学白求恩医学院病理生理教研室

收稿日期:2009-02-13 修回日期:2009-08-24 出版日期:2010-02-05 发布日期:2010-02-05
通讯作者: 李扬

Relationship between human membrane associated sialidase(Neu3) and multidrug resistance (MDR) in K562 cell line

Li XU, Lian-kun SUN, Feng LI, Bin YU, Xiao-jie LI, Xue-jian ZHAO, Yang LI

Department of Pathophysiology, Norman Bathune College of Medical Sciences, Jilin University

Received:2009-02-13 Revised:2009-08-24 Online:2010-02-05 Published:2010-02-05
Contact: Yang LI

摘要/Abstract

摘要： 目的探讨人质膜型唾液酸酶(Neu3)与人红白血病细胞多药耐药的关系。方法分别或联合柔红霉素(DNR)与唾液酸酶特异性抑制剂(NeuAC2en)处理K562和K562/ADM细胞，MTT法检测细胞生存率；RT-PCR检测MDR(多药耐药基因)、MRP(多药耐药相关蛋白)、MGMT(06-甲基鸟嘌呤-DNA甲基转移酶)、GST(谷胱甘肽S转移酶)、Bcl-xl、Bax和Bcl-2 mRNA表达；Western blot法检测P-gp(MDR基因蛋白产物：P-糖蛋白)蛋白表达；TBA法检测唾液酸酶活性。结果与K562细胞相比，K562/ADM细胞对DNR具有一定的抵抗性，NeuAC2en与DNR有协同作用(p﹤0.01)；应用NeuAC2en或DNR后K562和k562/ADM细胞Neu3活性均明显下降，两种药物联合应用Neu3活性下降最明显(P﹤0.01)；相同处理条件下，与K562细胞相比，K562/ADM细胞中Neu3、MDR1、Bcl-xl和Bcl-2表达增加，Bax无明显变化；应用DNR后，MDR1、Neu3、Bcl-xl、Bcl-2表达均下降，而DNR与NeuAC2en联合应用，以上基因表达水平下调最明显。结论 Neu3可能通过影响细胞凋亡和MDR1的表达从而增强肿瘤细胞的多药耐药性。

关键词: 人质膜型唾液酸酶, 多药耐药, K562

Abstract: Objective To investigate the role of human membrane associated sialidase (Neu3) in multidrug resistance (MDR) of K562 cells. Method K562 cells and K562/ADM cells were treated with DNR alone or the combination with DNR and NeuAC2en.The cells survival rate was measured by MTT assay; the expression of MDR related factors and apoptosis related factors, such as MDR, MRP, MGMT, GST, Bcl-xl, Bcl-2 and Bax were determined by western blot and RT-PCR; Neu3 activity was detected by TBA reaction. Result The survival rate of K562/ADM cells was higher than that of K562 cells; NeuAC2en showed synergistic effect with DNR(P<0.01); Neu3 activity of both K562 and K562/ADM cells decreased after DNR or NeuAC2en induction and the decrease degree was the most statistically significant in the combination treatment group(P<0.01). Under the identical condition, the protein expression of P-gp and Neu3 and the mRNA expression of MDR1, Neu3, Bcl-xl and Bcl-2 increased with comparison to K562 cells. The mRNA level of Bax in K562 and K562/ADM groups was not changed significantly. MDR1, Neu3,Bcl-xl and Bcl-2 decreased after DNR induction and down-regulated most obviously in the groups treated by DNR combined with NeuAC2en. Conclusion Neu3 may be related with multidrug resistance of K562/ADM cell through regulating apoptosis and the expression of MDR1.

Key words: human membrane-associated sialidase, MDR, K562

许莉孙连坤李峰禹彬李晓洁赵雪俭李扬. 人质膜型唾液酸酶与人红白血病细胞多药耐药相关[J]. 基础医学与临床, 2010, 30(2): 139-143.

Li XU; Lian-kun SUN; Feng LI; Bin YU; Xiao-jie LI; Xue-jian ZHAO; Yang LI. Relationship between human membrane associated sialidase(Neu3) and multidrug resistance (MDR) in K562 cell line[J]. Basic & Clinical Medicine, 2010, 30(2): 139-143.

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