硼替佐米联合三氧化二砷诱导急性髓性白血病细胞凋亡的体内外实验研究

扶云碧; 孟凡义; 李利; 孙启鑫

doi:10.13201/j.issn.1004-2806.2014.01.011

硼替佐米联合三氧化二砷诱导急性髓性白血病细胞凋亡的体内外实验研究

- 1 暨南大学医学院第四附属医院血液科(广州, 510220);
- 2 南方医科大学南方医院血液科

详细信息

通讯作者: 孟凡义,E-mail:mengfu@medmail.com.cn

中图分类号: R733.71

收稿日期: 2013-05-20

Anti-leukemic effect of bortezomib combined with arsenious acid in vitro and in vivo

- 1 Department of Hematology, the 4^th Hospital Affiliated to Medicine College of Jinan University, Guangzhou, 510220, China;
- 2 Department of Hematology, Nanfang Hospital of Southern Medical University

More Information

Corresponding author: MENG Fanyi, E-mail: mengfu@medmail.com.cn

Received Date: 20 May 2013

摘要

摘要: 目的:探讨蛋白酶体抑制剂硼替佐米单用及其与三氧化二砷(As₂O₃)联合作用,在体内外对急性髓性白血病HL60细胞的凋亡诱导作用。方法:MTT法检测细胞增殖抑制;Hoechst33342染色形态学观察证实细胞凋亡形态;流式细胞仪检测细胞凋亡率;建立移植瘤小鼠模型观察体内抑瘤作用,健康小鼠处理后观察毒副作用。结果:硼替佐米单用时对HL60细胞有明显的增殖抑制作用及凋亡诱导作用,As₂O₃与硼替佐米联合应用后对细胞的凋亡诱导明显增强。体内研究显示As₂O₃或硼替佐米单用均对小鼠HL60移植瘤生长有一定的抑制作用,二者联合应用能明显促进肿瘤体积缩小,但是毒副作用无明显增加。结论:硼替佐米单用在体内外均能抑制HL60细胞增殖,诱导凋亡,与As₂O₃联合应用后在体内外对HL60细胞增殖抑制与诱导凋亡作用均增强,但毒副作用无明显相加效应。
- 硼替佐米 /
- 三氧化二砷 /
- 急性髓性白血病 /
- HL60细胞 /
- 移植瘤
Abstract: Objective: To explore the apoptosis induced by bortezomib alone or combined with arsenious acid in HL60 cell line in vitro and in vivo.Method: Cell proliferation-inhibition was detected by MTT assay.Apoptosis morphology was demonstrated by Hoechst33342 staining.Apoptosis rate was detected by flow cytometry.Xenograft model of BALB/C-nu/nu mice were built and randomized into different treatment groups to observe the anti-tumor effect in vivo.To evaluate the toxicity of bortezomib combined with arsenious acid,body weight loss and WBCs were measured in healthy mice treated as in the xenograft model.Result: Bortezomib alone inhibited the proliferation of HL60 cells and induced cell apoptosis combined with arsenious acid,the pro-apoptotic effect significantly increased in vitro.Correspondingly,both arsenious acid and bortezomib alone inhibited the growth of the xenograft tumor of HL60.The tumor regressed in the group treated with bortezomib combined with arsenious acid,whereas the toxicity did not increase.Conclusion: Bortezomib alone can induce HL60 cells apoptosis in vitro and in vivo.Anti-tumor effect significantly enhances after bortezomib is combined with arsenious acid,whereas the toxicity is not obviously added.
- bortezomib /
- arsenious acid /
- acute myeloid leukemia /
- HL60 cells /
- mice xenograft model

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