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苦参碱通过bcr-abl介导的MEK-ERK通路抑制人慢性粒细胞白血病K562细胞增殖 被引量:5

Matrine suppresses the growth of human chronic myeloid leukemia K562 cells via inhibiting bcr-abl-mediated MEK-ERK pathway
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摘要 目的:探讨MEK-ERK通路在苦参碱抑制人慢性粒细胞白血病K562细胞增殖中的分子机制。方法采用Western blot法检测K562细胞内MEK-ERK通路关键分子MEK1、ERK1/2及其上游接头分子Shc、SHP2的总蛋白和磷酸化蛋白的表达;采用反转录聚合酶链反应(RT-PCR)和Western blot检测bcr-abl及有丝分裂原激活的蛋白激酶(MAPK)下游靶蛋白bcl-xL、Cyclin D1、c-myc及p27在转录及蛋白水平的表达。结果苦参碱可明显抑制K562细胞内MEK1、ERK1/2及Shc、SHP2的磷酸化表达,并可在转录及蛋白水平抑制bcr-abl分子表达。同时,RT-PCR和Western blot实验证实,苦参碱处理后,K562细胞内bcl-xL、Cyclin D1、c-myc表达均明显抑制,细胞周期负调控蛋白p27的表达增加。结论苦参碱对K562细胞的抑制效应与bcr-abl介导的MEK-ERK信号通路活性抑制有关,对信号通路中磷酸化蛋白或激酶分子活性的调控可能是其调控MEK-ERK通路活性的重要分子机制。 Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.
作者 何流漾 周海俊 孙晓 朱志超 白煜 蒋丽佳 卢绪章 周民 钱思轩 李建勇 马玲娣 He Liuyang, Zhou Haijun, Sun Xiao, Zhu Zhichao, Bai Yu, Jiang Lijia, Lu Xuzhang, Zhou Min, Qian Sixuan, Li Jianyong, Ma Lingdi (Department of Central Laboratory, Changzhou No.2 People's Hospital, Nanjing Medical University, Changzhou 213000, China)
出处 《肿瘤研究与临床》 CAS 2015年第7期433-437,444共6页 Cancer Research and Clinic
基金 国家自然科学基金(81101647) 南京医科大学科技发展基金重点项目(2010NJMUZ42) 南京医科大学博士后课题
关键词 苦参碱 白血病 粒细胞 慢性 MEK-ERK信号通路 bcr-abl Matrine Leukemia,myeloid,chronic MEK-ERK signaling pathway bcr-abl
作者简介 李建勇,Email:lijianyonglm@medmail.com.cn 通信作者:马玲娣,Email:lingdimawsh@126.com;
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