青蒿琥酯逆转CD7^+难治急性髓系白血病细胞对柔红霉素耐药作用的研究

Reverses Effect of Artesunate on Resistance of CD7^+ Refractory Acute Myeloid Leukemia Cells to Daunorubicin

目的:研究青蒿琥酯(artesunate,Art)逆转CD7^+难治急性髓系白血病(CD7^+AML)细胞对柔红霉素(daunorubicin,DNR)的耐药作用及其机制。方法:实验分为生理盐水对照组(NS组)、Art组(0、0.01、0.1、1μmol/L)、DNR组(0、0.02、0.2、2 mg/L)、Art(0、0.01、0.1、1μmol/L)+DNR(0、0.02、0.2、2 mg/L)联合组。Art、DNR、Art+DNR作用CD7^+AML细胞48 h后,CCK-8法检测细胞生长的抑制率,流式细胞术检测细胞凋亡率以及细胞内DNR含量,72 h后Western blot定量检测P170蛋白。结果:与单独应用Art或DNR相比,Art+DNR处理后,CD7^+AML细胞的抑制率、凋亡率和细胞内DNR含量均显著增加(P<0.05),而细胞内P170抗原表达显著降低(P<0.05)。结论:Art可通过下调CD7^+AML细胞P170抗原表达,增加细胞内DNR的药物浓度,从而增强疗效、逆转耐药。

Objective:To study the reverse effect of Artesunate(Art)on Daunorubicin(DNR)resistance in CD7^+ refractory acute myeloid leukemia(CD7^+AML)cells and its mechanism.Methods:The experiment was divided into NS group,art group(0,0.01,0.1,1μmol/L),DNR group(0,0.02,0.2,2 mg/L),art group(0,0.01,0.1,1μmol/L)+DNR group(0,0.02,0.2,2 mg/L).After CD7^+ AML cells were cultured with art,DNR and Art+DNR for 48 hours,CCK-8 method was used to detect the inhibition rate of cell growth,flow cytometry was used to detect the apoptosis rate and the content of DNR in cells,and Western blot was used to detect p170 protein expression.Results:Compared with Art or DNR alone,the inhibition rate,apoptosis rate and DNR content of CD7^+ AML cells increased significantly(P<0.05),while the expression of P170 antigen decreased significantly(P<0.05).Conclusion:Art can increase the concentration of DNR inCD7^+ AML cells by down regulating the expression of P170 antigen,so as to enhance the efficacy and reverse the drug resistance.