阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

张春; 陆晓彤; 陈敏玲; 张顺国; 王燕琼; 赵薇; 张健

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阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

张春, 陆晓彤, 陈敏玲, 张顺国, 王燕琼, 赵薇, 张健

文章导航 > 药学实践与服务 > 2010 > 28(4): 262-264,273

张春, 陆晓彤, 陈敏玲, 张顺国, 王燕琼, 赵薇, 张健. 阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异[J]. 药学实践与服务, 2010, 28(4): 262-264,273.

引用本文:

ZHANG Chun, LU Xiao-tong, CHEN Min-ling, ZHANG Shun-guo, WANG Yan-qiong, ZHAO Wei, ZHANG Jian. Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro[J]. Journal of Pharmaceutical Practice and Service, 2010, 28(4): 262-264,273.

Citation:

ZHANG Chun, LU Xiao-tong, CHEN Min-ling, ZHANG Shun-guo, WANG Yan-qiong, ZHAO Wei, ZHANG Jian. Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro[J]. Journal of Pharmaceutical Practice and Service, 2010, 28(4): 262-264,273.

阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

1.
上海交通大学医学院附属新华医院,上海200092
2.
上海交通大学医学院附属上海儿童医学中心,上海200127

Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro

1.
Xinhua Hospital offiliated to Shanghai Jiaotong University Medical School,Shanghai 200092,Chain
2.
Department of Pharmacy,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University Medical School,Shanghai 200127,China

摘要: 目的: 研究阿糖胞苷(cytarabine,Ara-C)或柔红霉素(daunorubicine,DNR)与全反式维A酸(all-trans retinoicacid,ATRA)以不同方式联用,体外作用于白血病细胞株HL-60,导致细胞凋亡差异及可能机制。 方法: 体外培养HL-60细胞株,细胞悬液以浓度2.0×10⁵/ml接种后分7组,分别为A:对照组;B:Ara-C与ATRA同时联用48 h组,Ara-C+ATRA48 h;C:ATRA与Ara-C先后联用48 h组,ATRA 24 h→Ara-C 24 h;D:Ara-C与ATRA先后联用48 h组,Ara-C 24 h→ATRA 24 h;E:DNR与ATRA同时联用48 h组,DNR+ATRA48 h;F:ATRA与DNR先后联用48 h组,ATRA24 h→DNR24 h;G:DNR与AT-RA先后联用48 h组,DNR 24 h→ATRA24 h。Ara-C、DNR、ATRA给药浓度均为1.0×10^-7mol/L。应用流式细胞仪、Westernblotting观察药物不同方式联用致HL-60细胞凋亡的差异及相关机制变化。 结果: 与A组相比,D组HL-60细胞凋亡比例轻度增加(50±14.7)%,抗凋亡蛋白Bcl-2消失;E组和G组HL-60凋亡细胞明显增多,其中E组能最大限度减少HL-60存活数量,使HL-60细胞死亡数目增加,达(4.00±0.56)%;E、F、G组抗凋亡蛋白Bcl-2均消失。 结论: 同时联用DNR与ATRA能显著减少HL-60细胞存活率,两药的三种联用方式均可使抗凋亡蛋白Bcl-2消失。但是,首先应用小剂量Ara-C,随后应用AT-RA的联用方式可明显增多细胞凋亡数目,抑制HL-60细胞的抗凋亡蛋白Bcl-2不能表达,有效控制细胞凋亡方向,是最有潜力的药物联用方式。
- 阿糖胞苷 /
- 柔红霉素 /
- 全反式维A酸 /
- HL-60 /
- 联用 /
- 凋亡 /
- 抗凋亡蛋白
Abstract: Objective To investigate variance of apoptosis and correspondingly mechanism in HL-60 cell line in vitro by different combinations adminstration of three drug including cytarabine,daunorubicin and all-trans retinoic acid.Methonds HL-60 cell line was cultured in vitro,cell suspension was divided into different 7 groups which's density was 2.0×10⁵/ml : Group A: control;Group B:Ara-C and ATRA were simultaneous applied in cells for 48 h(Ara-C+ATRA 48 h);Group C: ATRA and Ara-C subsequently administrated respectively for 24 h that is ATRA was applied first for 24 h,then followed by Ara-C for 24 h.Group D: Ara-C and ATRA subsequently administrated respectively for 24 h that is Ara-C was applied first for 24 h,then followed by ATRA for 24 h;Group E: DNR and ATRA simultaneously administrated for 48 h;Group F: DNR and ATRA subsequently administrated respectively for 24 h that is DNR was applied first for 24 h,then followed by ATRA for 24 h.Group G: ATRA and DNR subsequently administrated respectively for 24 h that is ATRA was applied first for 24 h,then followed by DNR for 24 h.All drug concentrations of Ara-C,DNR and ATRA were 1.0×10^-7 mol/L.The ratio of apoptosis cells was evaluated by flow cytometry.Anti-apoptosis protein Bcl-2 was checked by Western Blotting. Results The ratio of cell apoptosis in D group increase slightly,the rate of increase in apoptosis was(50±14.7) %,its protein Bcl-2 disappeared.Compared with control group,both two groups including E and G groups caused the apoptosis ratio significant higher.The alive cells' ratio in E group was reduced to the highest degree and the amount of dead cells increased to a degree of(4.00±0.56) %.Anti-apoptosis protein Bcl-2 in E,F,G groups all disappeared. Conclusion Combination DNR and ATRA simultaneously can effectively decrease HL-60 survival.Three ways of combination DNR with ATRA can signifi- cantly cause protein Bcl-2 disappear.But low dose of Ara-C was administrated first then followed by ATRA can not only increase slightly the ratio of apoptosis of HL-60 cell,but also inhibited anti-apoptosis protein Bcl-2 to express and effectively controled the way of HL-60 cell's death to apoptosis,and we concluded that this combination is the most potentiall way.
- cytarabine /
- daunorubicin /
- all-trans retinoic acid /
- HL-60 /
- combination /
- apoptosis /
- anti-apoptosis protein

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阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

1. 上海交通大学医学院附属新华医院,上海200092

2. 上海交通大学医学院附属上海儿童医学中心,上海200127

收稿日期: 2009-12-11
修回日期: 2010-01-11

关键词:

阿糖胞苷 /

柔红霉素 /

全反式维A酸 /

HL-60 /

联用 /

凋亡 /

抗凋亡蛋白

摘要: 目的: 研究阿糖胞苷(cytarabine,Ara-C)或柔红霉素(daunorubicine,DNR)与全反式维A酸(all-trans retinoicacid,ATRA)以不同方式联用,体外作用于白血病细胞株HL-60,导致细胞凋亡差异及可能机制。 方法: 体外培养HL-60细胞株,细胞悬液以浓度2.0×10⁵/ml接种后分7组,分别为A:对照组;B:Ara-C与ATRA同时联用48 h组,Ara-C+ATRA48 h;C:ATRA与Ara-C先后联用48 h组,ATRA 24 h→Ara-C 24 h;D:Ara-C与ATRA先后联用48 h组,Ara-C 24 h→ATRA 24 h;E:DNR与ATRA同时联用48 h组,DNR+ATRA48 h;F:ATRA与DNR先后联用48 h组,ATRA24 h→DNR24 h;G:DNR与AT-RA先后联用48 h组,DNR 24 h→ATRA24 h。Ara-C、DNR、ATRA给药浓度均为1.0×10^-7mol/L。应用流式细胞仪、Westernblotting观察药物不同方式联用致HL-60细胞凋亡的差异及相关机制变化。 结果: 与A组相比,D组HL-60细胞凋亡比例轻度增加(50±14.7)%,抗凋亡蛋白Bcl-2消失;E组和G组HL-60凋亡细胞明显增多,其中E组能最大限度减少HL-60存活数量,使HL-60细胞死亡数目增加,达(4.00±0.56)%;E、F、G组抗凋亡蛋白Bcl-2均消失。 结论: 同时联用DNR与ATRA能显著减少HL-60细胞存活率,两药的三种联用方式均可使抗凋亡蛋白Bcl-2消失。但是,首先应用小剂量Ara-C,随后应用AT-RA的联用方式可明显增多细胞凋亡数目,抑制HL-60细胞的抗凋亡蛋白Bcl-2不能表达,有效控制细胞凋亡方向,是最有潜力的药物联用方式。

English Abstract

Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro

1. Xinhua Hospital offiliated to Shanghai Jiaotong University Medical School,Shanghai 200092,Chain

2. Department of Pharmacy,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University Medical School,Shanghai 200127,China

Received Date: 2009-12-11
Rev Recd Date: 2010-01-11

Keywords:

Abstract: Objective To investigate variance of apoptosis and correspondingly mechanism in HL-60 cell line in vitro by different combinations adminstration of three drug including cytarabine,daunorubicin and all-trans retinoic acid.Methonds HL-60 cell line was cultured in vitro,cell suspension was divided into different 7 groups which's density was 2.0×10⁵/ml : Group A: control;Group B:Ara-C and ATRA were simultaneous applied in cells for 48 h(Ara-C+ATRA 48 h);Group C: ATRA and Ara-C subsequently administrated respectively for 24 h that is ATRA was applied first for 24 h,then followed by Ara-C for 24 h.Group D: Ara-C and ATRA subsequently administrated respectively for 24 h that is Ara-C was applied first for 24 h,then followed by ATRA for 24 h;Group E: DNR and ATRA simultaneously administrated for 48 h;Group F: DNR and ATRA subsequently administrated respectively for 24 h that is DNR was applied first for 24 h,then followed by ATRA for 24 h.Group G: ATRA and DNR subsequently administrated respectively for 24 h that is ATRA was applied first for 24 h,then followed by DNR for 24 h.All drug concentrations of Ara-C,DNR and ATRA were 1.0×10^-7 mol/L.The ratio of apoptosis cells was evaluated by flow cytometry.Anti-apoptosis protein Bcl-2 was checked by Western Blotting. Results The ratio of cell apoptosis in D group increase slightly,the rate of increase in apoptosis was(50±14.7) %,its protein Bcl-2 disappeared.Compared with control group,both two groups including E and G groups caused the apoptosis ratio significant higher.The alive cells' ratio in E group was reduced to the highest degree and the amount of dead cells increased to a degree of(4.00±0.56) %.Anti-apoptosis protein Bcl-2 in E,F,G groups all disappeared. Conclusion Combination DNR and ATRA simultaneously can effectively decrease HL-60 survival.Three ways of combination DNR with ATRA can signifi- cantly cause protein Bcl-2 disappear.But low dose of Ara-C was administrated first then followed by ATRA can not only increase slightly the ratio of apoptosis of HL-60 cell,but also inhibited anti-apoptosis protein Bcl-2 to express and effectively controled the way of HL-60 cell's death to apoptosis,and we concluded that this combination is the most potentiall way.

引用本文:

Citation:

ZHANG Chun, LU Xiao-tong, CHEN Min-ling, ZHANG Shun-guo, WANG Yan-qiong, ZHAO Wei, ZHANG Jian. Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro[J]. Journal of Pharmaceutical Practice and Service, 2010, 28(4): 262-264,273.

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阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro

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阿糖胞苷或柔红霉素与全反式维A酸的不同联用方式致体外HL-60凋亡差异

1. 上海交通大学医学院附属新华医院,上海200092 2. 上海交通大学医学院附属上海儿童医学中心,上海200127

English Abstract

Different administrations of combination cytarabine or daunorubicin with all-trans retinoic acid lead to variance of HL-60''s apoptosis and respectively mechanism in vitro

1. Xinhua Hospital offiliated to Shanghai Jiaotong University Medical School,Shanghai 200092,Chain 2. Department of Pharmacy,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University Medical School,Shanghai 200127,China

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1. 上海交通大学医学院附属新华医院,上海200092

2. 上海交通大学医学院附属上海儿童医学中心,上海200127

1. Xinhua Hospital offiliated to Shanghai Jiaotong University Medical School,Shanghai 200092,Chain

2. Department of Pharmacy,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University Medical School,Shanghai 200127,China