Xiao Xi-Bin, Xie Zhao-Xia, Chen Jie, Qin Qun, Zhu Yan
Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2005 Oct;30(5):558-61.
To explore the effect of neferine on the chemotherapic sensitivity of STI 571 to K562/A02 cells and to reveal its mechanism.
MTT method was used to observe the alteration of the proliferation of K562/A02 cell line treated with STI571 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.
The cytotoxic effect of STI 571 (1 micromol/L) combined with neferine (IC50 = 3.02 micromol/L) on K562/A02 cell line was significantly higher than that of STI 571 alone (IC50 = 0.689 micromol/L). After treating with STI571 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).
Neferine significantly enhances the antineoplastic effect of STI 571 on K562/A02 cells by reducing mdrl mRNA transcription and blocking P-gp expression.
探讨甲基莲心碱对STI 571作用于K562/A02细胞化疗敏感性的影响并揭示其机制。
采用MTT法观察单独使用STI571或联合甲基莲心碱处理K562/A02细胞系后细胞增殖的变化。采用半定量RT-PCR检测mdrl基因转录，并用蛋白质免疫印迹法测定单独使用STI 571或联合甲基莲心碱处理后P-糖蛋白的表达。
STI 571（1 μmol/L）联合甲基莲心碱（IC50 = 3.02 μmol/L）对K562/A02细胞系的细胞毒性作用显著高于单独使用STI 571（IC50 = 0.689 μmol/L）。STI571联合甲基莲心碱处理后，对K562/A02细胞的协同相互作用增加了4.38倍（P < 0.05）；半定量RT-PCR检测mdrl mRNA表达显著降低（45.4 ± 2.5）%（P < 0.01）；蛋白质免疫印迹法检测P-糖蛋白表达下调40.58%（P < 0.05）。
甲基莲心碱通过降低mdrl mRNA转录和阻断P-糖蛋白表达，显著增强STI 571对K562/A02细胞的抗肿瘤作用。
