摘要
目的:研究甲基莲心碱(Nef)在多药耐药白血病细胞K562/A02对STI571敏感性中的作用,并探讨其逆转耐药的机制。方法:MTT法比较STI571单独或与Nef联合应用对K562/A02细胞的抑制作用;RT-PCR法检测mdr1mRNA转录水平及WesternBlot法检测P-gp表达水平。结果:Nef与STI571联合应用对K562/A02细胞增殖的抑制作用明显增强。单独应用STI571对K562/A02细胞的IC50为3.02μmol/L,加Nef后,IC50为0.689μmol/L,逆转倍数为4.38倍(P<0.05)。STI571与Nef联合应用使mdr1mRNA转录水平下调(45.4±2.5)%(P<0.01),使P-gp的表达下调40.58%(P<0.05)。结论:甲基莲心碱能增强K562/A02细胞对STI571的敏感性,下调其mdr1mRNA的转录和阻断P-gp的表达,从而逆转白血病的多药耐药性。
Objective To explore the effect of neferine on the chemotherapic sensitivity of STI 571 to K562/A02 cells and to reveal its mechanism. Methods MTF method was used to observe the altera- tion of the proliferation of K562/A02 cell line treated with STI 571 alone or combined with neferine. The transcription of mdrl gene was detected by semi-quantitative RT-PCR and the P-gp expression was determined by Western blot after STI 571 alone or combined with neferine treatment. Results The cytotoxic effect of STI 571 ( 1μmol/L) combined with neferine (IC50 = 3.02 μmol/L) on K562/A02 cell line was significantly higher than that of STI 571 alone (IC50 =0. 689 μmol/L). After treating with STI 571 combined with neferine,the synergistic interaction on K562/A02 cells increased 4.38 folds (P 〈 0.05 ) ; the mdrl mRNA expression by semi-quantitative RT-PCR was significantly reduced by (45.4 ±2.5)% (P 〈 0.01 ) ; and the P-gp expression by Western blot was deregulated by 40.58% (P 〈0.05 ). Conclusion Neferine significantly enhances the antineoplastic effect of STI 571 on K562/A02 cells by reducing mdrl mRNA transcription and blocking P-gp expression.
出处
《中南大学学报(医学版)》
CAS
CSCD
北大核心
2005年第5期558-561,共4页
Journal of Central South University :Medical Science
基金
湖南省自然科学基金(03JJY5013)