摘要
目的探讨蛋白酶体抑制剂硼替佐米（Bor）单独或联合阿糖胞苷（Ara—C）对髓系白血病细胞系K562细胞增殖、凋亡的影响，并分析可能的作用机制。方法以20nmol／L的Bor、0．2μg/ml的Ara—C分别单独处理以及不同序贯方式联合处理K562细胞48h后，MTT法检测细胞生长抑制率；流式细胞术检测细胞凋亡率。并在两药分别单独处理6h后用sP免疫组化法分析细胞NF—KB活性及流式细胞术检测细胞周期的变化。结果不同方式联合用药组细胞生长抑制率与细胞凋亡率均高于两药分别单独处理组（P〈0．01），而且在各联合用药组中，先加入Ara—C预处理6h后再序贯加入Bor组的细胞生长抑制率和细胞凋亡率分别为（81．5±4．0）％和（29．2±3．1）％，均高于先加入Bor预处理6h后序贯Ara—C组[（54．1±4．2）％、（18．7±3．5）％]和同时加入组[（66．2±2．8）％、（21．1±2．2）％]（P〈0．01）。Bor单独处理细胞6h，细胞NF—κB活性减低，细胞阻滞于G2／M期；Ara—C单独处理细胞6h，NF—KB活性增高，G1期细胞明显增多。结论Bor呵有效抑制K562细胞增殖，并诱导其凋亡，与Ara—C联合，这种效应显著增强，尤以Ara—C预处理后序贯Bor组影响最大。Ara—C预处理后，对NF—κB及细胞周期的影响可能是发挥更大协同效应的原因。
Objective To investigate the effect of bortezomib （Bor） alone and in combination with arabinoside （Ara-C） on proliferation and apoptosis of leukemia cell line K562. Methods K562 ceils were treated with 20 nmol/L Bor and 0.2 μg/ml Ara-C alone and in combination for 48 h. MTT was used to study the inhibitory effects on cell growth and the apoptosis rate was analysed by flow cytometry. After K562 cells treated with 20 nmol/L Bor or 0.2 μg/ml Ara-C for 6 h, the activity of NF-κB was analyzed by SP immuno- histochemistry and cell cycle by flow cytometry. Results The inhibition and apoptosis rates of K562 cells in combination groups were higher than those in the two single treatment groups （P 〈 0. 01 ） , especially in the combined treatment group in which K562 cells were treated first with Ara-C for 6 h then with Bor combined, the inhibition and apoptosis rates were the highest [ （81.5 ± 4.0）% and （29.2± 3. 1 ）%, respectively] （ P 〈 0.01 ）. In the other two combined groups in which the cells were treated with Bor for 6 h then with Ara- C combined, or treated with the two drugs simultaneously, the inhibition and apoptosis rates were （54.1 ± 4.2）% and （18.7±3.5）%, and （66.2±2.8）% and （21.1±2.2）%, respectively. Treatment ofK562 cells with 20 nmoL/l, Bor for 6 h, the activity of NF-KB was decreased significantly, and the cells were appar- ently arrested in GJM phase, and treatment with 0.2 μg/ml Ara-C in the same manner, the activity of NF- KB was increased significantly, and the cells were apparently arrested in G1 phase. Conclusions Bor can effectively inhibit K562 cell proliferation, and indueed its apoptosis. This effect was enhanced signifieantly when in combination with Ara-C. Pretreatment of K562 ceils with Ara-C lead to the increased activity of NF- κB and the fraction of G1 phase cells.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2010年第1期42-45,共4页
Chinese Journal of Hematology
