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。
Objective：To explore the apoptosis induced by bortezomib alone or combined with arsenious acid in HL60cell line in vitro and in vivo.Method：Cell proliferation-inhibition was detected by MTT assay.Apoptosis morphology was demonstrated by Hoechst33342staining.Apoptosis rate was detected by flow cytometry.Xeno- graft 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 pro- liferation of HL60cells and induced cell apoptosis combined with arsenious acid,the pro-apoptotic effect signifi- cantly 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 HL60cells 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.
出处
《临床血液学杂志》
CAS
2014年第1期35-39,共5页
Journal of Clinical Hematology
