摘要
目的:观察环孢素A(CsA)处理急性单核细胞白血病细胞株THP-1后对柔红霉素(DNR)的耐药性及与多药耐药相关蛋白-1(MRP1)表达的关系,探讨CsA对THP-1细胞的化疗增敏作用及相关机制。方法:噻唑蓝(MTT)法、荧光分光光度法、共聚焦激光扫描显微镜(CLSM)法分别检测CsA处理前后50% THP-1细胞生长受抑的DNR浓度(IC50)、THP-1细胞内DNR含量及分布的变化。免疫细胞化学法、Western blot法检测CsA处理前后THP-1细胞MRP1蛋白表达量的变化。结果:CsA处理后THP-1细胞的IC50明显下降(1.5364±0.1751 vs 0.5588±0.0547,P<0.01),细胞内DNR含量明显增加(21.40±1.71 vs 131.96±16.45,P<0.01),且胞浆内分布更加均匀;同时MRP1蛋白表达量增高(0.2665±0.0042 vs 0.3169±0.0062,P<0.01)。结论:CsA可增加THP-1细胞对DNR的敏感性,降低其耐药性,并提示CsA对THP-1细胞耐药性的改变不是通过降低其MRP1蛋白表达量来实现的。
Objective：To observe the changes of resistance to daunorubicin （DNR） and the expression of multidrug resistance associated protein-1 （MRP1） in acute monocytic leukemia cells THP-1 treated by cyclosporin A （CsA）, and explore CsA＇s function on chemotherapy sensitization to THP-1 cells as well as the related mechanism. Methods：IC50 of DNR to THP-1 cells, content and distribution of DNR in THP-1 cells treated by CsA were examined by MTF method and confocal laser scanning microscopy method, respectively. Expression amount of MRP1 were detected by immunocytochemistry and Western blot. Results：After treated with CsA, ICs0 decreased obviously （1.536 4±0.175 1 vs 0.558 8 ±0.054 7,P 〈 0.01）, content of DNR increasing obviously （21.40 ± 1.71 vs 131.96±16.45, P 〈 0.01）, DNR distributing uniformly, and expression of MRP1 increased （0.266 5 ±0.004 2 vs 0.316 9± 0.006 2,P 〈 0.01）. Conclusion： CsA can increase the sensibility of THP-1 cells to DNR, not through decreasing the expression of MRP1 in THP-1 cells. This might show that the resistance of THP-1 cells to DNR can＇t be reduced by inhibiting the activity of MRP.
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2009年第8期1071-1076,共6页
Journal of Nanjing Medical University(Natural Sciences)
关键词
CSA
细胞株
THP-1
增敏作用
MRP1蛋白
cyclosporin A
cell line,THP-1
aensitization
muhidrug resistance associated protein-1
