西罗莫司对Raji细胞增殖、凋亡影响的研究  

Effects of sirolimus on growth and apoptosis of cell Raji

作　　者：江莲[1] 白涛敏[2] 刘翠萍[1] 朱秀丽[1] 陈健[1] 

机构地区：[1]河北医科大学第四医院儿科,石家庄050011 [2]陕西省人民医院儿科,西安710068

出　　处：《中国小儿血液与肿瘤杂志》2015年第5期237-244,共8页Journal of China Pediatric Blood and Cancer

基　　金：河北省卫生厅重点科技研究计划(编号20090148)

摘　　要：目的探讨西罗莫司对恶性淋巴瘤细胞的作用及其可能机制。方法实验分为西罗莫司组、阿霉素组、西罗莫司+阿霉素组、对照组,观察各组人非霍奇金淋巴瘤Raji细胞增殖、凋亡及细胞周期分布情况,应用MTT比色法检测细胞生长情况,流式细胞术(FCM)分析细胞凋亡及细胞周期分布的情况;应用FCM和免疫细胞化学染色法检测HIF-1α蛋白在西罗莫司各组中的表达情况。结果(1)西罗莫司和阿霉素对Raji细胞生长具有抑制作用,且在一定范围内呈时间剂量依赖性;(2)西罗莫司+阿霉素组吸光度值(A492)与西罗莫司组、阿霉素组相比差异均有显著性(P<0.05);(3)西罗莫司+阿霉素组凋亡率与对照组、阿霉素组相比差异均有显著性(P<0.05),与西罗莫司组相比差异无显著(P>0.05);(4)西罗莫司+阿霉素组各期细胞比例与对照组、阿霉素组相比,细胞周期分布发生明显变化(P<0.05),与西罗莫司组差异无显著性(P>0.05)。(5)西罗莫司各浓度组HIF-1α蛋白表达率下降,与对照组相比差异有显著性(P<0.05)。结论西罗莫司体外对Raji细胞生长具有明显的抑制作用。西罗莫司通过阻滞Raji细胞G0/G1期抑制Raji细胞增殖,通过下调HIF-1α蛋白的表达诱导Raji细胞凋亡。西罗莫司与阿霉素联合对Raji细胞生长具有明显抑制作用,优于单用西罗莫司,但对Raji细胞凋亡和周期的影响与单用西罗莫司无显著差异。Objective To investigate the effects of Sirolimus on the proliferation,apoptosis,cell cycle distribution and HIF-1α expression in human malignant lymphoma cell line Raji and the possible anti-tumor mechanism of Sirolimus.Methods The experiment was divided into 4 groups：control group,Sirolimus group,Adriamycin（ADM） group and Sirolimus ＋ ADM group.Cell inhibitive rate was tested by MTT assay.Apoptosis rate,cell cycle distribution and expression of HIF-la protein in Raji cells were detected by FCM and immunocytochemistry.Results ①The survival of Raji cells was inhibited by Sirolimus and ADM in vitro with a concentration and time dependent manners in a circumscription.② The absorbance of the group treated with Sirolimus ＋ ADM for 48 hours was significantly different compared with the group treated with the same concentration of Sirolimus or ADM（P 0.05）.③ The apoptosis rate between the Sirolimus ＋ ADM group and control group or ADM group was remarkable difference（P 0.05）,but there was no remarkable difference between this group treated with Sirolimus of the same concentration（P 0.05）.④ Compared with control group or ADM group,the cell cycle distribution of the group treated with Sirolimus ＋ ADM for 48 hours existed significant difference（P0.05）,but it had no difference with the group treated with the same concentration of Sirolimus alone（P 0.05）.⑤HIF-1αprotein expression in various concentrations of Sirolimus group was significantly different,compared with the control group（P 0.05）.Conclusions ① The survival of Raji cells was obviously inhibited by Sirolimus in vitro.② Sirolimus induced cell cycle arrested in G0/G1 phase and inhibited the growth of Raji cells.Raji cells treated with Sirolimus ＋ ADM was conspicuous repressed compared with Raji cells treated with Sirolimus or ADM respectively.There was no significandy difference between the group treated with Sirolimus ＋ ADM and the groups treated with Sirolimus individually.

关 键 词：西罗莫司 淋巴瘤 细胞周期 凋亡 低氧诱导因子-1Α 

分 类 号：R96[医药卫生—药理学]