ABCG2对多发性骨髓瘤侧群细胞及相关通路的作用

Effect of ABCG2 on Side Population Cells and Related Pathways in Multiple Myeloma

目的:探讨ABCG2的生物学特性及其对多发性骨髓瘤(MM)侧群细胞(side population cells,SP cells)的作用,以探究逆转药物耐药的办法。方法:利用siRNA干扰多发性骨髓瘤细胞,使ABCG2表达沉默。对比干扰前后多发骨髓瘤侧群(SP)细胞比例、细胞增殖速度、细胞对化疗药物敏感性,进一步了解ABCG2的生物学功能及其在调控多发骨髓瘤侧群细胞及PTEN/PI3K/AKT信号通路发挥的作用。结果:siRNA干扰可以下调ABCG2的表达,干扰后的MM细胞ABCG2在mRNA及蛋白水平上表达明显降低。siRNA干扰后MM细胞增殖能力略有减弱,PTEN表达升高,PI3K/AKT通路活性受到抑制,SP细胞比例降低,同时细胞对化疗药物的反应能力增强。结论:在多发性骨髓瘤中,ABCG2的下调可负反馈上调PTEN的表达,PI3K/AKT信号通路受抑,SP比例下调,增强药物敏感性。

Objective:To investigate the biological characteristics of ABCG2 and its effect on side population cells(SP cells)of multiple myeloma(MM)so as to find the way for reversing drug resistance.Methods:The silence of ABCG2 expression was performed throngh interfering the MM cells by using siRNA.then the ratio of SP cell of MM,speed of cell proliferation and sensitivity of cells to chermotherapentic drugs before and after interference were compared,the biological functions of ABCG2 and its role in regulation of SP cells and PTEN/PI3 K/AKT signaling pathway was clarified.Results:siRNA interference could down regulate the expression of ABCG2 at both mRNA and protein level.After siRNA interference,the proliferation of multiple myeloma cells was decreased slightly,the expression of PTEN was increased,the activity of PI3 K/AKT pathway was inhibited,and the ratio of SP cells was decreased.Conclusion:In multiple myeloma,down-regulation of expression ABCG2 can negatively regulate the expression of PTEN,the PI3K/AKT signaling pathway is inhibited,the ratio of SP decreased,and the response to drug is increased.