MAPK途径磷酸化在胰岛素样生长因子1促进人骨髓瘤细胞株KM3增殖.docVIP

MAPK途径磷酸化在胰岛素样生长因子1促进人骨髓瘤细胞株KM3增殖 　 作者：王华芳，胡豫，孙春艳，王雅丹 【摘要】 本 研究 探讨胰岛素样生长因子1（IGF1）对人骨髓瘤细胞株KM3增殖的 影响 以及MAPK途径磷酸化在该过程中的作用。采用流式细胞术检测不同浓度的重组人IGF1处理后KM3细胞周期的变化，Western blot法检测细胞内MAPK信号转导途径主要分子Erk1/2磷酸化在IGF1刺激及PD98059特异性抑制作用下的改变， TUNEL法检测特异性阻断Erk1/2磷酸化在抑制KM3细胞增殖和诱导凋亡中的作用。 结果表明， IGF1可以显著提高S期和G2/M期的KM3细胞比率和细胞内Erk1/2分子的磷酸化水平，阻断IGF1引起的Erk1/2磷酸化可以显著抑制KM3细胞的增殖并引起其凋亡。结论： IGF1引起的Erk1/2分子磷酸化在KM3细胞增殖过程中起着十分重要的作用。 【关键词】 骨髓瘤 毕业论文 Effect of MAPK Signaling Pathway Phosphorylation on Proliferation of Myeloma Cell Line KM3 by Insulinlike Growth Factor 1 Abstract In order to study the effect of insulinlike growth factor 1 (IGF1) on proliferation of myeloma cell line KM3 and the role of MAPK pathway phosphorylation in this process, the cell cycle distribution shift of KM3 after incubation with series concentration of IGF1 was detected by flow cytometry. PhosphorateErk1/2, the key molecule of MAPK pathway, was examined by Western blot after KM3 cells bEing pretreated with or without PD98059, the special inhibitor of Erk1 and Erk2 phosphorylation. The effect of specifically blocking Erk1 and Erk2 phosphorylation on proliferation and apoptosis of KM3 cells were detected with TUNEL staining. The results showed that the KM3 cells at S and G2/M phase increased and the phosphorylation of Erk1 and Erk2 became intensive when incubated with different concentration of IGF1. PD98059 could decrease the phosphorylation of Erk1/2 induced by IGF1 and induce the apoptosis of KM3 cells. It is concluded The phosphorylation of MAPK signaling pathway trigged by IGF1 plays an important role in the proliferation of myeloma cell line KM3. 毕业论文 Key words IGF1；MAPK pathway；Erk 1/2 phosphorylation; multiple myeloma 多发性骨髓瘤（multiple myeloma, MM）在恶性血液系统疾病中发病率居第二位，其发病机制尚不清楚。胰岛素样生长因子1（insulinlike growth factor I , IGF1）与多发性骨髓瘤细胞的增殖密切相关，它不仅刺激多发性骨髓瘤细胞的分裂，增殖和转移，还具有抑制地塞米松诱导的细胞凋亡、刺激肿瘤自身分泌血管内皮生长因子等多种作用［1-5］。本研究探讨与多发性骨髓瘤细胞增殖关系密切的丝裂原活化蛋白激酶（mitogenactivated protEIn kinase, MAPK）信号途径在I