摘要
目的:研究治疗bcr-abl和mdrl共同阳性的白血病的新方法。方法:采用MTT法检测酪氨酸激酶抑制剂STI571(1 μmol/L)分别与浓度为10-4、10-5、10-6、10-7、10-8mol/L的长春新碱(VCR)、柔红霉素(DNR)、高三尖杉酯碱(HHT)及DNR+阿糖胞苷(Ara-C)(浓度为1 mmol/L)联合应用对bcr-abl和mdrl共同阳性的裸鼠高致瘤性人白血病细胞系K562-n/VCR的作用。结果:不同浓度的VCR单独应用及与STI571联合应用IC50分别为127.28μmol/L、1.37 μmol/L,协同倍数为93.04倍;不同浓度的DNR单独应用及与STI571联合应用IC50分别为6.96μmol/L、0.30 μmol/L,协同倍数为23.25倍;不同浓度的HHT单独应用及与STI571联合应用IC50分别为156.70μmol/L、7.916μmol/L,协同倍数为19.80倍;不同浓度的DNR+Ara-C单独应用及与STI571联合应用IC50分别为0.10 μmol/L、0.015 μmol/L,协同倍数为464倍,化疗药物与STI571联合应用细胞毒作用明显增强。结论:化疗药物VCR、DNR、DNR+Ara-C与STI571等联合应用对于bcr-abl与mdr1共同阳性的白血病细胞较单独应用有更强的抑制作用。
Purpose: To study new treatment of leukemia with both bcr-abl and mdrl positive. Methods: We detected the effect of STI571 ( 1 μmol/L), an inhibitor of tyrosine kinase, in combination respectively with vincristine (VCR), daunorubicin (DNR), homoharringtonin( HHT) ( 10-4,10-5, 10-6, 10-7,10-8 mol/L) and DNR + arabinoside cytosine (Ara-C) of 1 mmol/L on a high tumorigenicity in nude mice multi drug-resistant leukemia cell line ( K562-n/VCR) by MTT method. Results: IC50 of VCR and VCR + STI571 were 127.28 μmol/L, 1. 37 μmol/L respectively, and synergistic interaction on K562-n/VCR cells was 93. 04-fold. IC50 of DNR and DNR + STI571 were 6. 96μmol/L, 0. 30μmol/L respectively, synergistic interaction was 23. 35-fold. IC50 of HHT and HHT + STI571 were 156.70μmol/L, 7.916μmol/L respectively, synergistic interaction was 19. 80-fold. IC50 of DNR + Ara-C and DNR + Ara-C + STI571 were 0. 10 μmol/L, 0. 015 μmol/L respectively, the synergistic interaction was 464-fold. Chemotheraputic agents have not intensive cytotoxic effect on K562-n/VCR cells, but the cytotoxic effect became greater when combined with STI571. Conclusions: Combination of STI571 with DNR, VCR, HHT and DNR + Ara-C had a greater synergistic inhibiting effect on K562-n/ VCR cells . The combinations of STI571 and these Chemotheraputic agents would display synergistic activity in bcr-abl and mdrl positive leukemia cells.
出处
《中国癌症杂志》
CAS
CSCD
2004年第2期154-156,共3页
China Oncology
基金
国家自然科学基金资助项目(39770330)。
