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| LC 促进人成骨样 MG-63 细胞增殖及相关机制的研究 |
| Molecular mechanism of LC in promoting the proliferation of human osteoblast-like cells MG-63 |
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| DOI： |
| 中文关键词: 大黄酸哌嗪雌酚酮(LC) 人成骨细胞 MG-63 增殖 雌激素受体 |
| 英文关键词:Ｒhein-piperizinyl-estrone Human osteoblasts MG-63 Proliferation Estrogen receptor |
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| 中文摘要: |
| 目的 探讨大黄酸哌嗪雌酚酮(rhein-piperizinyl-estrone，LC)对人成骨样 MG-63 细胞增殖活性的影响及其相关分子机制。方法 在原工作基础上，以兼有两种雌激素受体(estrogen receptor，EＲ) 亚型表达的人成骨样 MG-63 细胞为研究对象，分别应用 MTT 法和流式细胞术，观察 LC 对 MG-63 细胞的增殖活性和细胞周期分布的影响。利用前期构建的 EＲα 或 EＲβ 稳定高抑制表达的 MG-63 细胞株，应用免疫印迹技术，对 LC 的作用机制和可能的信号通路进行研究。结果 与对照组相比，LC
可明显促进 MG-63 细胞的增殖活性，该作用具有剂量依赖性;可调节细胞周期分布，使 G1 期细胞比例减少、G2 + S 期细胞比例增加，进而促进细胞生长。进一步研究发现，EＲ 阻断剂 ICI 182，780 可完全阻断 LC 的促增殖作用，提示 LC 是经 EＲ 途径对
MG-63 的增殖活性发挥作用的;利用 EＲα 或 EＲβ 高抑制表达的稳定细胞株，证实 LC 的促增殖作用是由 EＲα 和 EＲβ 共同介导的;该作用与 Ｒas/MEK/EＲK、PI3K/Akt 信号通路的激活密切相关。结论 LC 可经 EＲα 和 EＲβ 共同介导对人成骨细胞的促增殖作用，有望成为治疗绝经后骨质疏松症的新型骨靶向雌激素类药物。 |
| 英文摘要: |
| Objective To investigate the molecular mechanism of rhein-piperizinyl-estrone (LC) on regulating the proliferation of
human osteoblast-like MG-63 cells． Methods Based on our previous studies，human osteoblast-like MG-63 cell line expressing
endogenous EＲα and EＲβ was selected as the model for this study． The effect of LC on the proliferation and cell cycle distribution of MG-63 cells was studied using MTT assay and FACS technology． MG-63/EＲα shＲNA，MG-63/EＲβ shＲNA，and MG-63/scrambled shＲNA stable cell lines were used to study the related signal pathways with Western blotting assay． Ｒesults LCincreased proliferation of human osteoblastic MG-63 cells by altering cell cycle distribution． Treatment with the EＲ antagonist ICI182，780 abolished the above action of LC on MG-63 cells． Using the MG-63/EＲα shＲNA，MG-63/EＲβ shＲNA，and MG-63/scrambled shＲNA stable cell lines，we further demonstrated that the effect of LC on proliferation was mediated by both EＲα andEＲβ． Moreover，we demonstrated that the regulation of osteoblastic proliferation by LC involved Ｒas/MEK/EＲK and PI3K/Akt
signaling． Conclusion LC promotes the proliferation of osteoblasts through both EＲα and EＲβ，which may become a new estrogen-targeting drug for the treatment of postmenopausal osteoporosis． |
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