白血病细胞核因子-κB活化与化疗药物诱导凋亡的关系

Relation between activation of NF-κB and chemotherapy induced apoptosis of leukemic cells

目的 研究化疗药物诱导P388白血病细胞核因子 κB (NF κB)活化与凋亡的关系 ,以及长春新碱 (VCR)对它们的影响。方法 采用电泳迁移率变动分析 (EMSA)检测细胞NF κB活化水平 ;采用TdT介导的dUTP缺口末端标记技术 (TUNEL)和DNA电泳方法检测细胞凋亡。结果 化疗药物诱导P388白血病细胞NF κB活化与化疗药物诱导细胞凋亡有明显关系 ,0 .1μmol LVCR不仅能显著抑制 10 0 μmol L阿糖胞苷 (Ara C)或 10 0 μmol L鬼臼乙叉甙 (Vp 16 )诱导的P388细胞NF κB活化 (抑制率分别为 5 2 %和 6 3% ) ,而且增强它们诱导P388细胞凋亡的作用 (凋亡增加率分别为 89%和 12 3% )。P388细胞在接触化疗药物前 ,NF κB亦有一定程度的活化。结论 化疗药物诱导P388白血病细胞凋亡的同时 ,可活化NF κB ;VCR可通过抑制NF κB活化 ,增强化疗药物诱导白血病细胞凋亡的作用。

Objective To analyze the relation between activation of NF κB and chemotherapy induced apoptosis of leukemic cells and the effect of vincristine (VCR) on them. Methods Electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF κB and tunel DNA electrophoresis was adopted to observe the apoptosis induced by cytosine arabinoside (Ara C) and etopside (Vp 1 6) in P388 leukemic cells. Results The activation of NF κB induced by Ara C and Vp 16 was obviously correlated to apoptosis in P388 cells. VCR ( 0.1 μmol/L ) could suppress activation of NF κB by 52% and 63% and significantly increase the apoptosis by 89% and 123% as induced by Ara C(100 μmol/L) and Vp 16(100 μmol/L). The activity of NF κB could be found in P388 cells before being exposed to chemotherapeutic agent. Conclusion Chemotherapeutic agents can induce apoptosis and activation of NF κB of P388 cells. The mechanism of VCR potentiating chemotherapeutics induction of leukemia cell apoptosis may be related to its suppression of the NF κB activaty in the P388 cells. [