Li Guang-Yao, Liu Ji-Zhu, Zhang Bin, Wang Le-Xin, Wang Chun-Bo, Chen Shou-Guo
Division of Hematology, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province 252000, PR China.
Biomed Pharmacother. 2009 Sep;63(8):566-70. doi: 10.1016/j.biopha.2008.10.008. Epub 2008 Dec 6.
This study was designed to investigate the effects of cyclosporine A (CsA) on a multidrug resistance cultured cell line, and its effect on complete remission in patients with acute myeloid leukemia (AML). A multidrug resistant K562/ADM cell line and drug-sensitive K562 cell line was used. The intracellular concentration of daunorubicin and the accumulation of Rhodamine 123 (Rh123) in the K562/ADM and K562 cells were evaluated. Clinical effects of CsA were also studied in 65 patients with AML. In the K562/ADM cells, the 50% of inhibition concentration (IC50) of daunorubicin only group was 23.0+/-5.2 micromol/L, which was greater than in other groups co-administered with CsA (1.2+/-4.8 micromol/L), verapamil (1.5+/-5.4 micromol/L) or CsA+verapamil (1.4+/-4.3 micromol/L) (all P<0.01). The relative fluorescence intensity of Rh123 in the K562/ADM cells treated with CsA and daunorubicin was increased from 48.9% to 69.8% (P<0.05). CsA also improved the complete remission rate in the AML patients (72.7% vs 21.9%, P<0.01). We conclude that CsA can significantly diminish the multidrug resistance in K562/ADM cells. It also enhances the complete remission rates in patients with AML. CsA may be used as an integral part of the chemotherapy for AML.
本研究旨在探讨环孢素A（CsA）对多药耐药培养细胞系的影响及其对急性髓系白血病（AML）患者完全缓解的影响。使用了多药耐药的K562/ADM细胞系和药物敏感的K562细胞系。评估了柔红霉素在K562/ADM和K562细胞中的细胞内浓度以及罗丹明123（Rh123）的蓄积情况。还对65例AML患者研究了CsA的临床效果。在K562/ADM细胞中，单纯柔红霉素组的50%抑制浓度（IC50）为23.0±5.2微摩尔/升，高于与CsA（1.2±4.8微摩尔/升）、维拉帕米（1.5±5.4微摩尔/升）或CsA+维拉帕米（1.4±4.3微摩尔/升）联合使用的其他组（均P<0.01）。用CsA和柔红霉素处理的K562/ADM细胞中Rh123的相对荧光强度从48.9%增加到69.8%（P<0.05）。CsA还提高了AML患者的完全缓解率（72.7%对21.9%，P<0.01）。我们得出结论，CsA可显著降低K562/ADM细胞中的多药耐药性。它还提高了AML患者的完全缓解率。CsA可作为AML化疗的一个组成部分。
