多柔比星对人骨肉瘤细胞P-糖蛋白表达的影响  

Effect of Doxorubicin on P-glycoprotein Expression in Human Osteosarcoma Cells

作　　者：叶天宝 张振宇 王伯仁 王大昊 Ye Tianbao;Zhang Zhenyu;Wang Boren;Wang Dahao(The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000 China)

机构地区：[1]锦州医科大学附属第一医院,辽宁锦州121000

出　　处：《锦州医科大学学报》2022年第3期53-56,共4页Journal of Jinzhou Medical University

基　　金：辽宁省科学技术计划项目,项目编号:2012225071。

摘　　要：目的观察多柔比星(doxorubicin,DOX)对人骨肉瘤细胞凋亡及核转录因子NF-κB、多药耐药蛋白P-gp表达的影响。方法体外培养人骨肉瘤U2-OS细胞系,分别用0、1、5、10和100μg/mL的多柔比星作用于人骨肉瘤U2-OS细胞24、48、72 h后,用MTS法测定细胞增殖活性,用流式细胞仪检测细胞凋亡率,用Western blot方法检测不同浓度多柔比星作用于骨肉瘤U2-OS细胞24 h后各组细胞的NF-κB和P-gp蛋白表达水平。结果多柔比星在体外能抑制人骨肉瘤U2-OS细胞增殖(P<0.05),其对人骨肉瘤U2-OS细胞的生长抑制率随多柔比星浓度增加、时间延长呈剂量及时间依赖性;多柔比星能够诱导骨肉瘤U2-OS细胞凋亡(P<0.05),凋亡率随多柔比星浓度增加、时间延长呈剂量及时间依赖性;同时,Western blot方法检测发现不同浓度多柔比星作用于人骨肉瘤U2-OS细胞24 h后,随多柔比星浓度增加,NF-κB和P-gp蛋白表达水平逐渐上调(P<0.05)。结论多柔比星能够抑制人骨肉瘤U2-OS细胞增殖,并诱导人骨肉瘤U2-OS细胞凋亡,同时,多柔比星能够诱导人骨肉瘤U2-OS细胞多药耐药P-gp蛋白表达上调,其机制可能与多柔比星激活核转录因子NF-κB蛋白表达有关。Objective In this study,we observed the effect of doxorubicin on the apoptosis of human osteosarcoma cells and the expression of NF-κB and P-gp protein.Methods The human osteosarcoma U2-OS cell line was cultured in vitro.The human osteosarcoma U2-OS cells were treated with doxorubicin at 0,1,5,10 and 100μg/mL for 24 h,48 h and 72 h,respectively.MTS method was used to determine the cell proliferation activity,flow cytometry was used to detect the apoptosis rate of the cells,and Western blot was used to detect the protein expression levels of NF-κB and P-gp in U2-OS cells treated with doxorubicin at different concentrations for 24 h.Results Doxorubicin could inhibit the proliferation of human osteosarcoma U2-OS cells in vitro(P<0.05),and the growth inhibition rate of doxorubicin was dose-dependent and time-dependent with the increase of doxorubicin concentration and the extension of time.Doxorubicin could induce the apoptosis of U2-OS cells in osteosarcoma(P<0.05),and the apoptosis rate was dose-dependent and time-dependent with the increase of doxorubicin concentration and the extension of time.Meanwhile,Western blot analysis showed that the expression levels of NF-κB and P-gp protein were gradually up-regulated with the increase of doxorubicin concentration in human osteosarcoma U2-OS cells for 24 h after doxorubicin concentration increased(P<0.05).Conclusion Doxorubicin can inhibit the proliferation and induce the apoptosis of human osteosarcoma U2-OS cells.At the same time,doxorubicin can up-regulate the multidrug resistance of human osteosarcoma U2-OS cells,which may be related to the expression of NF-κB activated by doxorubicin.

关 键 词：多柔比星 骨肉瘤细胞 细胞凋亡 NF-ΚB P-GP 

分 类 号：R738.1[医药卫生—肿瘤]