中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2010年
1期
42-45
,共4页
硼替佐米%阿糖胞苷%K562细胞%细胞周期%NF-κB
硼替佐米%阿糖胞苷%K562細胞%細胞週期%NF-κB
붕체좌미%아당포감%K562세포%세포주기%NF-κB
Bortezomib%Arabinoside%K562 cell line%Cell cycle%NF-κB
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20 nmoL/L的Bor、0.2μg/ml的Ara-C分别单独处理以及小同序贯方式联合处理K562细胞48 h后,MTT法检测细胞生长抑制率;流式细胞术榆测细胞凋亡率.并在两药分别单独处理6 h后用SP免疫组化法分析细胞NF-κB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6 h后冉序贯加入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6 h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6 h,细胞NF-κB活性减低,细胞阻滞于G_2/M期;Ara-C单独处理细胞6 h,NF-κB活性增高,G_1期细胞明显增多.结论 Bor可有效抑制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及细胞剧期的影响可能足发挥更大协同效应的原因.
目的 探討蛋白酶體抑製劑硼替佐米(Bor)單獨或聯閤阿糖胞苷(Ara-C)對髓繫白血病細胞繫K562細胞增殖、凋亡的影響,併分析可能的作用機製.方法以20 nmoL/L的Bor、0.2μg/ml的Ara-C分彆單獨處理以及小同序貫方式聯閤處理K562細胞48 h後,MTT法檢測細胞生長抑製率;流式細胞術榆測細胞凋亡率.併在兩藥分彆單獨處理6 h後用SP免疫組化法分析細胞NF-κB活性及流式細胞術檢測細胞週期的變化.結果不同方式聯閤用藥組細胞生長抑製率與細胞凋亡率均高于 兩藥分彆單獨處理組(P<0.01),而且在各聯閤用藥組中,先加入Ara-C預處理6 h後冉序貫加入Bor組的細胞生長抑製率和細胞凋亡率分彆為(81.5±4.0)%和(29.2±3.1)%,均高于先加入Bor預處理6 h後序貫Ara-c組[(54.1±4.2)%、(18.7±3.5)%]和同時加入組[(66.2±2.8)%、(21.1±2.2)%](P<0.01).Bor單獨處理細胞6 h,細胞NF-κB活性減低,細胞阻滯于G_2/M期;Ara-C單獨處理細胞6 h,NF-κB活性增高,G_1期細胞明顯增多.結論 Bor可有效抑製K562細胞增殖,併誘導其凋亡,與Ara-C聯閤,這種效應顯著增彊,尤以Ara-C預處理後序貫Bor組影響最大.Ara-C預處理後,對NF-κB及細胞劇期的影響可能足髮揮更大協同效應的原因.
목적 탐토단백매체억제제붕체좌미(Bor)단독혹연합아당포감(Ara-C)대수계백혈병세포계K562세포증식、조망적영향,병분석가능적작용궤제.방법이20 nmoL/L적Bor、0.2μg/ml적Ara-C분별단독처리이급소동서관방식연합처리K562세포48 h후,MTT법검측세포생장억제솔;류식세포술유측세포조망솔.병재량약분별단독처리6 h후용SP면역조화법분석세포NF-κB활성급류식세포술검측세포주기적변화.결과불동방식연합용약조세포생장억제솔여세포조망솔균고우 량약분별단독처리조(P<0.01),이차재각연합용약조중,선가입Ara-C예처리6 h후염서관가입Bor조적세포생장억제솔화세포조망솔분별위(81.5±4.0)%화(29.2±3.1)%,균고우선가입Bor예처리6 h후서관Ara-c조[(54.1±4.2)%、(18.7±3.5)%]화동시가입조[(66.2±2.8)%、(21.1±2.2)%](P<0.01).Bor단독처리세포6 h,세포NF-κB활성감저,세포조체우G_2/M기;Ara-C단독처리세포6 h,NF-κB활성증고,G_1기세포명현증다.결론 Bor가유효억제K562세포증식,병유도기조망,여Ara-C연합,저충효응현저증강,우이Ara-C예처리후서관Bor조영향최대.Ara-C예처리후,대NF-κB급세포극기적영향가능족발휘경대협동효응적원인.
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 cells 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 effeets 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 immunohistochemistry and cell cycle by flow eytometry.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 of K562 cells with 20 nmol/L Bor for 6 h,the activity of NF-κB was decreased significantly,and the cells were apparently arrested in G_2/M phase,and treatment with 0.2μg/ml Ara-C in the sanle manner,the activity of NF-κB was increased significantly,and the cells were apparently arrested in G_1 phase.Conclusions Bor Can effeetively inhibit K562 cell proliferation.and induced its apoptosis.This effect was enhanced significantly when in combination with Ara-C.Pretreatment of K562 cells with Ara-C lead to the increased activity of NF-κB and the fraction of G_1 phase cells.
