国际输血及血液学杂志
國際輸血及血液學雜誌
국제수혈급혈액학잡지
INTERNATIONAL JOURNAL OF BLOOD TRANSFUSION AND HEMATOLOGY
2008年
4期
317-320,316
,共5页
陈为志%刘传方%李丽珍%安立%衣翠华
陳為誌%劉傳方%李麗珍%安立%衣翠華
진위지%류전방%리려진%안립%의취화
NF-κB%survivin基因%MG132%白血病
NF-κB%survivin基因%MG132%白血病
NF-κB%survivin기인%MG132%백혈병
NF-κB%survivin gene%MG132%Leukemia acute
目的 观察MG132对初治、复发及耐药急性白血病细胞体外诱导凋亡作用及NF-κB活性改变对survivin基因表达的影响.方法 分别采集32例(初治12例、复发10例及耐药10例)急性白血病患者骨髓,经Ficoll分离出单个核细胞体外培养,加入不同浓度的MG132培养24 h,Annexin V-FITC检测细胞凋亡,Western blotting和RT-PCR法检测NF-κB p65和survivin的表达.结果 不同浓度的MG132可诱导初治、复发及耐药急性白血病细胞发生凋亡,且呈剂量依赖效应.NF-κB活性和survivin表达在初治组和复发组、初治组和耐药组之间有显著性差异(P<0.01),但在复发组和耐药组间无显著性差异(P>0.05).survivin表达与NF-κB活性密切正相关(Pearson相关系数为0.957,P<0.01),survivin表达随着NF-κB活性被抑制而下调.结论 MG132在体外可以通过选择性抑制NF-κB活性诱导初治、复发及耐药急性白血病细胞凋亡,并下调抗凋亡基因survivin的表达.
目的 觀察MG132對初治、複髮及耐藥急性白血病細胞體外誘導凋亡作用及NF-κB活性改變對survivin基因錶達的影響.方法 分彆採集32例(初治12例、複髮10例及耐藥10例)急性白血病患者骨髓,經Ficoll分離齣單箇覈細胞體外培養,加入不同濃度的MG132培養24 h,Annexin V-FITC檢測細胞凋亡,Western blotting和RT-PCR法檢測NF-κB p65和survivin的錶達.結果 不同濃度的MG132可誘導初治、複髮及耐藥急性白血病細胞髮生凋亡,且呈劑量依賴效應.NF-κB活性和survivin錶達在初治組和複髮組、初治組和耐藥組之間有顯著性差異(P<0.01),但在複髮組和耐藥組間無顯著性差異(P>0.05).survivin錶達與NF-κB活性密切正相關(Pearson相關繫數為0.957,P<0.01),survivin錶達隨著NF-κB活性被抑製而下調.結論 MG132在體外可以通過選擇性抑製NF-κB活性誘導初治、複髮及耐藥急性白血病細胞凋亡,併下調抗凋亡基因survivin的錶達.
목적 관찰MG132대초치、복발급내약급성백혈병세포체외유도조망작용급NF-κB활성개변대survivin기인표체적영향.방법 분별채집32례(초치12례、복발10례급내약10례)급성백혈병환자골수,경Ficoll분리출단개핵세포체외배양,가입불동농도적MG132배양24 h,Annexin V-FITC검측세포조망,Western blotting화RT-PCR법검측NF-κB p65화survivin적표체.결과 불동농도적MG132가유도초치、복발급내약급성백혈병세포발생조망,차정제량의뢰효응.NF-κB활성화survivin표체재초치조화복발조、초치조화내약조지간유현저성차이(P<0.01),단재복발조화내약조간무현저성차이(P>0.05).survivin표체여NF-κB활성밀절정상관(Pearson상관계수위0.957,P<0.01),survivin표체수착NF-κB활성피억제이하조.결론 MG132재체외가이통과선택성억제NF-κB활성유도초치、복발급내약급성백혈병세포조망,병하조항조망기인survivin적표체.
Objective To investigate the apoptosis induced by MG132(Z-LLL-CHO, one kind of proteasome inhibitors) in vitro in newly diagnosed, relapsed and muhi-drug resistant (MDR) acute leukemia and the effect of NF-κB activation on survivin gene expression. Methods Bone marrow cells of 32 acute leukemia eases (12 newly diagnosed eases, 10 relapsed eases, and 10 multi-drug-resistant eases) w ere isolated with Ficoll's method and euhured in vitro. After 24-hours' acting by MG132, cell apoptosis was analyzed by Annexin V-FITC. The NF-κB and survivin expression was analyzed by Western blotting and RT-PCR. Results Different concentration of MG132 can induce the dose-dependent apoptosis in leukemia cells from newly diagnosed, relapsed and MDR acute leukemia. Highly abnormal expression of survivin and NF-κB was down regulated after the acting of MG132. As a result, expression of survivin was significantly different between the newly diagnosed and the relapsed or between the newly diagnosed and the MDR eases(P＜0. 01), but was not significantly different between the relapsed and the MDR ones(P ＞ 0. 05). Downregulation of survivin expression was closely correlated with the inhibition of NF-κB activation (Pearson correlation coefficien r = 0. 957, P＜ 0. 01). Conclusion MG132 can induce the leukemia cell apoptosis in vitro. Downregulation of survivin expression was closely correlated with the inhibition of NF-κB activation.
