摘要
目的:研究青蒿琥酯逆转K562/A02细胞对阿霉素的耐药性及其作用机制。方法:以对阿霉素敏感的K562细胞作为对照,用MTT法观察在有或无阿霉素存在条件下青蒿琥酯对培养的K562/A02细胞干预48 h后的生长抑制情况,流式细胞仪检测100μg.m l-1青蒿琥酯作用48 h前后K562/A02细胞P糖蛋白(P-gp)平均荧光强度(MFI)的强弱,生化方法检测100μg.m l-1青蒿琥酯作用48 h前后K562/A02细胞内谷胱甘肽(GSH)的含量。结果:(1)在不含阿霉素情况下,青蒿琥酯对K562及K562/A02细胞的IC50分别为13.80μg.m l-1和13.62μg.m l-1(P>0.05),在阿霉素存在情况下,青蒿琥酯对K562/A02细胞抑制作用明显增加(P<0.01);(2)与K562细胞P-gp的表达相比,K562/A02细胞P-gp高表达,青蒿琥酯处理前后K562/A02细胞的MFI无差别(P>0.05);(3)青蒿琥酯处理后K562/A02细胞内GSH含量较处理前明显下降(P<0.05)。结论:青蒿琥酯对K562及K562/A02细胞具有细胞毒作用,且可逆转K562/A02细胞对阿霉素的耐药,其机制可能是通过干扰细胞内GSH-GSH-s-转移酶系统功能的发挥,而非对P-gp表达的影响。
Objective To study the reversal effects of artesunate on the muhidrug-resistant cell line K562/A02 Methods (1)K562/A02 and sensitive K562 cells were treated with artesunate at different conditions, IC50 values of the drug was analyzed by MTF at 48 h ; (2) The expression of P-gp concentration in K562/A02 cells after 48 h treated with 100 μg·ml^-1 artesunate was detected by flow cytometry; (3) The glutathione concentration was examined by bio- chemical analyses. Results ( 1 ) Without adriamycin,the IC50 of artesunate on K562 was 13.8 μg·ml^-1 ,that on K562/ A02 was 13.62 Iμg·ml^-1 ;with adriamycin,the IC50 of artesunate on K562/A02 was 2.64 μg·ml^-1. (2) K562/A02 cells displayed high levels of P-glycoprotein compared to their parental K562 cells, artesunate 100 μg·ml^-1 had no effect on the levels of P-gp expression in K562/A02 cells ( P 〉0.05) ; (3) Cellular GSH concentration in K562/A02 cells treated with artesunate 100 μg·ml^-1 for 48 h [ (65. 040 ± 10. 674) mg · ( mg pro) ^-1 ] was lower than that in K562/A02 cell line [ ( 143.210 ± 25. 344 ) mg · ( mg pro) ^-1 ] without drugs ( P 〈 0. 05 ) . Conclusion Not only does artesunate has the cytotoxicity on K562 and K562/A02 ,but can also reverse the muhidrug resistance of K562/A02. The mechanism is that artesunate interferes with the function of glutathione-glutathione s-transferases, not the expression of P-gp.
出处
《东南大学学报(医学版)》
CAS
2006年第6期445-447,共3页
Journal of Southeast University(Medical Science Edition)