柴胡皂苷-d促进骨肉瘤细胞凋亡的研究  

The study of saikosaponin-d promotes apoptosis of osteosarcoma cells

作　　者：庄怡富 干耀恺[1] 汤亭亭[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院骨科上海市骨科内植物重点实验室,200011

出　　处：《国际骨科学杂志》2017年第2期115-120,共6页International Journal of Orthopaedics

摘　　要：目的探讨柴胡皂苷-d(SS-d)对骨肉瘤Saos-2细胞增殖、凋亡、迁移和侵袭能力的影响,并探讨其作用机制。方法经不同浓度SS-d处理骨肉瘤Saos-2细胞后,采用八肽胆囊收缩素(CCK-8)法检测骨肉瘤细胞增殖情况,采用流式细胞术检测骨肉瘤细胞凋亡情况,采用Transwell小室法检测骨肉瘤细胞迁移和侵袭能力,最后采用蛋白质免疫印迹(Western blot)法探讨SS-d对核因子-κB(NF-κB)/丝裂原活化蛋白激酶(MAPK)信号转导通路的作用及其下游凋亡相关蛋白的影响。结果 SS-d可呈剂量依赖性地明显抑制骨肉瘤Saos-2细胞的增殖、迁移和侵袭能力(P均<0.05),促进骨肉瘤Saos-2细胞凋亡(P<0.05)。SS-d可抑制p-IκBα和p-p65表达,下调p-Jnk和p-p38表达,进而抑制NF-κB/MAPK信号转导通路激活,促进下游凋亡相关蛋白Bax和裂解活化的半胱氨酸天冬氨酸蛋白酶(cleaved caspase)-3表达,减小Bcl-2/Bax比值,促进骨肉瘤Saos-2细胞凋亡。结论 SS-d可明显抑制骨肉瘤Saos-2细胞增殖、迁移和侵袭,促进骨肉瘤Saos-2细胞凋亡。这一现象与SS-d抑制NF-κB/MAPK信号转导通路激活,减小Bcl-2/Bax比值,促进cleaved caspase-3表达有关。Objective To investigate the effect of saikosaponin-d（SS-d）on the proliferation,apoptosis,migration and invasion of the osteosarcoma Saos-2 cells,and the related mechanism.Methods Osteosarcoma Saos-2 cells were treated with varying concentrations of SS-d.CCK-8 analysis was used to evaluate the proliferation ability of Saos-2 cells;flow cytometry was employed to investigate the apoptosis ability;Transwell Chamber assay was utilized to explore the migration and invasion ability.Next,Western blot was used to assess the effect of SS-d on activation of nuclear factor-κB（NF-κB）/mitogen-activated protein kinase（MAPK）pathways and the downstream apoptosis-related proteins.Results SS-d dose-dependently inhibited osteosarcoma Saos-2 cell proliferation,migration and invasion（P〈0.05）while promoted apoptosis（P〈0.05）.Western blot revealed that SS-d could inhibit the expressions of p-IκBαand p-p65,reduce the production of p-Jnk and p-p38,contributing to the inhibition of activated NF-κB/MAPK signaling,the elevated expressions of apoptosis-related proteins Bax and cleaved caspase-3 with decreased Bcl-2/Bax ratio,and the apoptosis of osteosarcoma Saos-2 cells.Conclusion SS-d was capable of downregulating osteosarcoma Saos-2 cells proliferation,migration and invasion,upregulating osteosarcoma Saos-2 cells apoptosis.These effects might be associated with the inhibition of NF-κB/MAPK signaling,decreased Bcl-2/Bax ratio and increased cleaved caspase-3 by SS-d treatment.

关 键 词：骨肉瘤 柴胡皂苷-D 细胞凋亡 核因子-κB/丝裂原活化蛋白激酶信号转导通路 BCL-2/BAX 

分 类 号：R285[医药卫生—中药学]