槲皮素对慢性髓系白血病伊马替尼耐药细胞株的作用及机制研究  

Effects of Quercetin on Chronic Myeloid Leukemia Cell Line Resistant to Imatinib and Its Mechanism

作　　者：卢虹颖 陈娟[1] 杜圣红[1] 贾培敏[1] 童建华[1,2] 吴英理[3] 周励[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科,上海血液学研究所,上海200025 [2]上海交通大学医学院检验系,上海200025 [3]上海交通大学医学院病理生理学教研室细胞分化与凋亡教育部重点实验室,上海200025

出　　处：《中国实验血液学杂志》2017年第2期346-352,共7页Journal of Experimental Hematology

摘　　要：目的:探讨槲皮素对慢性髓系白血病伊马替尼耐药细胞株的生长抑制作用及其机制。方法:台盼蓝染色法检测细胞活力,流式细胞术检测细胞凋亡和细胞周期,Western blot检测相关蛋白的表达水平。结果:25μmol/L槲皮素对伊马替尼耐药的K562细胞株K562R和K562G具有与伊马替尼敏感细胞株K562相似的生长抑制和诱导凋亡作用,且不改变BCR-ABL的表达水平。25μmol/L槲皮素处理24 h后,K562、K562R和K562G细胞的G_2/M期百分比明显增加。槲皮素能使γ-H2AX水平明显增高,且上调JNK的磷酸化水平。结论:槲皮素单药对伊马替尼耐药细胞株具有生长抑制和诱导凋亡作用,使细胞停滞于G_2/M期,其机制可能与上调JNK磷酸化水平导致DNA双链损伤相关。Objective： To explore the growth inhibitory effect of quercetin on imatinib-resistant chronic myeloid leukemia cell lines and to clarify its involved mechanisms. Methods： The cell viability was detected by trypan blue Staining, percentage of apoptotic cells and cell cycle distribution were detected by flow cytometry, the protein expression was detected by Western blot. Results ： Both inhibitory effect of proliferation and apoptosis-inducing effect were similar between the imatinib-resistant and -sensitive cell lines treated with 25μmol/L quercetin for 24 hours and with arrest of cell cycle at G2/M phase. Quercetin could not change the expression of BCR-ABL. The expression of γ-H2AX was markedly enhanced and the phosphorylation of JNK up-regulated by quercetin in both imatinib-resistant and imatinib-sensitive cell lines. Conclusion： The growth of imatinib-resistant cells can be inhibited by quercetin, and the apoptosis of cells can be induced by quercetin, which may be related to cell cycle arrest in G2/M. The DNA damage and up-regula- tion of p-JNK may be involved in these processes.

关 键 词：慢性髓系白血病 槲皮素 伊马替尼耐药 细胞周期阻滞 DNA损伤 JNK 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]