上海交通大学学报（医学版）

›› 2009, Vol. 29 ›› Issue (10): 1187-.

• 论著（基础研究） • 上一篇    下一篇

三氧化二砷诱导骨髓瘤细胞JAK/STAT3通路抑制作用的研究

王鸣明, 邹丽芳, 窦红菊, 朱 琦, 任志宏, 胡钧培   

  1. 上海交通大学 医学院第九人民医院血液内科 上海血液学研究所, 上海 200011
  • 出版日期:2009-10-25 发布日期:2009-10-26
  • 通讯作者: 胡钧培, 电子信箱: hujunpei90@hotmail.com。
  • 作者简介:王鸣明（1981—）, 女, 住院医师, 硕士；电子信箱: mingming.wang205198@gmail.com。
  • 基金资助:

    上海交通大学医学院院基金课题（05XJ21023）

Arsenic trioxide induced JAK/STAT3 pathway inhibition in myeloma cell lines

WANG Ming-ming, ZOU Li-fang, DOU Hong-ju, ZHU Qi, REN Zhi-hong, HU Jun-pei   

  1. Department of Hematology, The Ninth People's Hospital, Shanghai Institute of Hematology, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China
  • Online:2009-10-25 Published:2009-10-26
  • Supported by:

    Shanghai Jiaotong University School of Medicine Foundation, 05XJ21023

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摘要：

目的 研究三氧化二砷（As2O3)诱导人骨髓瘤细胞U266、RPMI8226细胞内JAK/STAT3信号转导通路抑制与细胞增殖之间存在的关系。方法 采用MTT法观察As2O3对骨髓瘤细胞作用的半数抑制浓度（IC50），流式细胞技术检测As2O3作用前后细胞周期的改变情况，甲基化特异性PCR法检测As2O3作用前后骨髓瘤细胞内SOCS-1基因甲基化状态的变化，Western blotting法检测As2O3作用前后磷酸化STAT3蛋白的表达差异。结果 As2O3作用72 h后，骨髓瘤细胞U266、RPMI8226细胞内磷酸化STAT3蛋白表达水平明显降低，同时伴随SOCS-1基因启动子区CpG岛甲基化程度明显减弱至消失，细胞增殖发生G0/G1期阻滞，上述三者变化均与As2O3浓度呈正相关（r=0.85，P<0.05）。结论 As2O3可诱导骨髓瘤细胞增殖受抑，与As2O3诱导细胞内JAK/STAT3信号转导通路抑制存在一定关系，且与细胞内SOCS-1基因甲基化状态改变相关。

关键词: 砷剂, 骨髓瘤, SOCS-1基因, JAK/STAT3, 细胞周期

Abstract:

Objective To explore the possible relationship between alteration of cell cycle and JAK/STAT3 signal transduction pathway inhibition induced by arsenic trioxide (As2O3) in myeloma cell lines U266 and RPMI8226 in vitro. Methods Multiple myeloma cell lines U266 and RPMI8226 were used as in vitro models. The influence of As2O3 on myeloma cells were evaluated by MTT assay and flow cytometry. Meanwhile, methylation specific PCR and Western blotting were employed to detect the methylation status of gene SOCS-1 and protein expression level of P-STAT3 in these cells after As2O3 treatment. Results As2O3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. Furthermore, cell cycle was arrested at G0/G1 phase with inhibition of protein expression level of P-STAT3 and SOCS-1 gene demethylation after exposure to As2O3 for 72 h（r=0.85, P<0.05）. Conclusion As2O3 could induce the alteration of cell cycle which might be related to JAK/STAT3 signal transduction pathway inhibition and SOCS-1 demethylation in myeloma cell lines. The study puts forward a new idea of As2O3 treatment in multiple myeloma.

Key words: arsenic trioxide, myeloma, SOCS-1, JAK/STAT3, cell cycle

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