硒化壳聚糖通过下调核因子КB途径增强ST1571对耐药K562/ADM细胞敏感性

Effect of Selenium Chiston on Enhancing Chemotherapic Sensitivity of ST1571 to Human Leukemia multidrug resistance Cell Line K562 /ADM Through Down Regulating Nuclear FactorКB Pathway

目的研究硒化壳聚糖增强ST1571对多药耐药白血病K562/ADM细胞敏感性的作用,并进一步探讨其耐药逆转机制。方法应用MTT法检测ST1571单独和联合硒化壳聚糖对K562/ADM细胞增殖的影响,计算逆转倍数;应用流式细胞法检测细胞凋亡;应用免疫印迹法检测核因子КB(NF-КB)蛋白的改变。结果单独应用1μmol·L-1ST1571作用12,24,36 h,对K562/ADM细胞增殖抑制率分别为(19.15±1.64)%、(24.35±2.37)%和(26.37±2.39)。1μmol·L-1ST1571联合25~400 mg·L-1硒化壳聚糖作用K562/ADM细胞,随着硒化壳聚糖浓度和作用时间的增加,对细胞增殖抑制率也相应增加,呈剂量时间效应关系。硒化壳聚糖能够对K562/ADM细胞耐ST1571产生一定的逆转作用,明显增强ST1571对K562/ADM细胞的诱导凋亡作用(P<0.05,P<0.01),下调NF-КB蛋白表达(P<0.01)。结论硒化壳聚糖能够增强K562/ADM细胞对ST1571的敏感性,其部分机制可能是通过诱导细胞凋亡,抑制细胞mdr-1基因表达,阻断细胞NF-КB信号通路来实现的。

Objective To Study the effect of Selenium chiston （Sc） on enhancing chemotherapic sensitivity of ST1571 to human leukemia muhidrug resistance K562/ADM cells in vitro and discuss the possible correlative mechanism. Methods The Prolifera- tion inhibitory rate of ST1571 alone or combination with Sc on K562/ADM cell line was determined by MT＇F and the reversal index was calculated. The apoptosis rate was examined by Flow cytometry . The expression of Nuclear FactorKB protein was detected by Western Blot. Results The Proliferation inhibitory rate was （ 19.15 ＋ 1.64） %, （ 24.35 ＋ 2.37 ） % and （ 26.37 ~ 2.39 ） % respec- tively after treated with 1 p^mol ~ L-i ST1571 for 12,24,36h in K562/ADM cells and the inhibitory rates was significantly in-