摘要
目的研究热休克蛋白90(Hsp90)抑制剂新生霉素(novobiocin,NB)对STI571耐药K562/G01细胞生长的抑制作用,并研究NB和STI571联合应用对STI571敏感和耐药细胞的作用,并进一步探讨该作用与Bcr-Abl蛋白水平和Bcr-Abl激酶水平的关系。方法用MTT法检测NB对K562和K562/G01细胞生长的抑制作用,用金氏公式评价药物合用体外是否有协同作用,用蛋白免疫印迹法检测Bcr-Abl蛋白水平和p-Tyrosine水平。结果NB能抑制K562和K562/G01细胞增殖,IC50分别是0.4353mmol.L-1和0.3490mmol.L-1;NB和STI571联合应用对STI571敏感和耐药细胞均有协同作用;NB能使K562和K562/G01细胞内Bcr-Abl和p-Tyrosine蛋白含量减少。结论NB通过减少Bcr-Abl和p-Tyrosine蛋白含量,抑制STI571耐药细胞K562/G01的增殖,NB和STI571有协同效应。
Aim To confirm the effects of Hsp90 inhibitor NB on STI571 resistant K562/G01 cells, and reveal the effect of combination of NB and STI571 on STI571 sensitive or resistant cells;to further clarify the relationship between growth inhibition and Bcr-Abl protein level and its kinase activity. Methods The viability of K562/G01 cells was examined by MTT; the effect of combination of NB and STI571 was valued by Jin＇s formula; the abundance of Bcr-Abl and p-Tyrosine was determined by Western blot. Results NB was a potent inhibitor of proliferation of K562 and K562/G01 cells with IC50 values of 0. 4353 mmol·L^-1 and 0. 3490 mmol·L^-1, respectively ; cotreatment with NB and STI571 exerted synergistic growth inhibition of K562 and K562/G01 cells. NB down-regulated Bcr-Abl and p-Tyrosine levels markedly. Conclusion NB was able to down-regulate Bcr-Abl and p-Tyrosine protein levels, resulting in inhibition of the growth of STI571 resistant K562/G01 cells ;NB and STI571 exerted synergistic effects.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第12期1556-1560,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30171158
30472187)
福建省自然科学基金资助项目(NoC0610025)
福建省科技厅三项费资助项目
