目的 研究尼洛替尼(nilotinib，AMN107诱导K562/A02细胞凋亡及对血红素加氧酶-1(HO-1基因表达的影响。方法 采用荧光原位杂交(FISH法检测K562/A02细胞中的BCR-ABL融合基因；用不同浓度的AMN107分别处理K562/A02细胞24 h后，通过实时荧光定量PCR(RQ-PCR法检测BCR-ABL融合基因mRNA的表达水平；采用MTT法观察细胞增殖变化；通过Annexin V/PI双染色法检测细胞凋亡和细胞周期；采用RT-PCR法和Western Blot法检测HO-1基因的表达。 结果 FISH法分析结果显示，K562/A02细胞BCR-ABL融合基因阳性细胞占细胞总数98%；RQ-PCR法检测结果显示，0，5，10，20 μmol·L-1 AMN107作用于K562/A02细胞24 h后BCR-ABL融合基因表达随AMN107浓度增加而逐渐下降；MTT法和Annexin V/PI法显示与对照组相比，细胞存活率随AMN107浓度升高而下降，凋亡率逐渐增加；细胞周期分析显示，经AMN107处理的细胞，G₀/G₁期和S期细胞明显减少，细胞阻滞在G₂/M期；RT-PCR法和Western blot法均检测到HO-1基因表达随AMN107浓度升高而降低。结论 AMN107可抑制BCR-ABL融合基因和HO-1基因表达，从而诱导慢性粒细胞白血病（CML耐药细胞的凋亡，说明HO-1是CML细胞生长以及BCR-ABL基因存在的一个相关因子，HO-1基因是克服慢性粒细胞白血病耐药的一个潜在靶向。

OBJECTIVE To investigate the effect of nilotinib on HO-1 gene expression and induction of apoptosis in K562/A02 cells. METHODS BCR-ABL in K562/A02 cell was detected by Fluorescence in situ hybridization (FISH. K562/A02 cells were treated with AMN107 of different concentrations for 24 h. The expression of BCR-ABL gene on mRNA level was detected by RQ-PCR. Cell proliferation was observed by MTT. Cell apoptosis and cell cycle were inspected by Annexin V/PI double staining method. The expression of HO-1 gene was determined using RT-PCR and Western Blot. RESULTS Ninety-eight percent of K562/A02 cells was detected with BCR-ABL fusion gene by FISH. RQ-PCR results showed that BCR-ABL fusion gene had a dose-dependent relationship with AMN107 in K562/A02 cells treated by AMN107 (0, 5, 10 and 20 μmol·L-1 for 24 h. MTT and Annexin V/PI tests showed that survival rate of treated cells was negatively associated with the concentrations of AMN107, while the apoptosis rate was positively associated. Cell cycle analysis showed that the number of cells in G₀/G₁ phase decreased sharply and the cell cycle arrested at G₂/M checkpoint in AMN107 treated cells. RT-PCR and Western blot tests indicated that the expression of HO-1 gene decreased negatively with increasing concentration of AMN107. CONCLUSION AMN107 can inhibit the expression of BCR-ABL and HO-1, which may be the mechanism underlying AMN107-induced apoptosis of drug-resistant CML cells. The results indicats that HO-1 is a key factor related with the growth of CML cells and the existence of BCR-ABL gene, and it may be a novel target for overcoming resistance of CML.