摘要
目的探讨β-榄香烯(β-elemene)对白血病细胞的耐药逆转及其对聚腺苷二磷酸聚合酶(PARP)和P-糖蛋白(P-gp)表达的影响。方法取对数生长期人类髓系白血病K562细胞的柔红霉素(DNR)耐药株K562/DNR及其敏感株K562细胞,采用台盼蓝拒染法测定其对β-榄香烯的药物敏感性及耐药逆转,采用流式细胞术PI染色检测细胞凋亡,采用流式细胞术检测细胞内药物累积,Western blot检测蛋白PARP和P-gp的表达,应用SPSS(13.0软件包)进行统计学分析。结果β-榄香烯明显抑制K562和K562/DNR细胞的生长,呈剂量依赖关系。低毒剂量(5μg/mL)β-榄香烯作用K562/DNR细胞,显著提高了柔红霉素的细胞毒作用,IC50降低至(0.68±0.43,P<0.05),逆转倍数为1.91倍。与柔红霉素单药组相比,加入低毒剂量β-榄香烯后,细胞药物蓄积明显增加(P<0.05)。β-榄香烯作用后诱导PARP裂解,同时下调了P-gp蛋白表达。结论β-榄香烯部分逆转K562/DNR细胞对柔红霉素的耐药性,其逆转机制与增加细胞内药物的蓄积、诱导PARP裂解及降低P-gp的表达有关。
Objective To explore the reversing effect of β-elemene on the multi-drug resistance of leukemia cells and the expressions of poly-ADP-ribose polymerase protein(PARP) and P-glycoprotein(P-gp) in K562/DNR cells.Methods Trypanblue dye exclusion method was used to detect the sensitivity of K562/DNR cells to β-elemene and the reversing effect of β-elemene on multi-drug resistance.Cell apoptosis was determined by flow cytometry after propidium iodide staining.Intracellular accumulation of daunorubicin in K562/DNR cells was observed by fluorescent-spectrophotometry.Expressions of the proteins were detected by Western blot.All experiment data were dealt with by SPSS(13.0 software package).Results The inhibitory effect of β-elemene on both K562 and K562/DNR was detected in a dose-dependent manner.Low-cytotoxic dose of β-elemene could obviously decrease the IC50 value of K562/DNR cells to daunorubicin(IC50=0.68±0.43,P<0.05).The reversing fold was 1.91.Low-cytotoxic dose of β-elemene could evidently increase the intracellular accumulation of daunorubicin and remarkably induce the activated fragment of PARP and decrease P-gp expression in K562/DNR cells.Conclusion β-elemene can partially reverse the multi-drug resistance of K562/DNR cells to daunorubicin,which is related to the increased accumulation of intracellular drugs,the activated fragment of PARP and the decreased expression of P-gp.
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2011年第6期664-667,共4页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.30901736)
辽宁省教育厅一般项目(No.L2010641)~~
关键词
白血病
Β-榄香烯
多药耐药
聚腺苷二磷酸聚合酶
柔红霉素
细胞凋亡
leukemia cell
β-elemene
multi-drug resistance
poly-ADP-ribose polymerase protein(PARP)
daunorubicin(DNR)
apoptosis
