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胡文勇 莫金君 李军 李璐华 王卫国.Wnt-beta-catenin信号通路对骨肉瘤细胞化疗敏感性研究[J].现代生物医学进展英文版,2015,15(29):5633-5636.
Wnt-beta-catenin信号通路对骨肉瘤细胞化疗敏感性研究
Wnt-beta-catenin Signaling Pathway on the Sensitivity to Chemotherapy ofOsteosarcoma Cells
  
DOI:
中文关键词: 骨肉瘤  甲氨喋呤  凋亡
英文关键词: Osteosarcoma  Methotrexate  Apoptosis
基金项目:四川省教育厅科学技术研究项目(2011658)
Author NameAffiliation
胡文勇 莫金君 李军 李璐华 王卫国 四川凉山彝族自治州第一人民医院骨科中南大学湘雅三医院骨科 
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中文摘要:
      目的:分析Wnt-beta-catenin 信号通路在骨肉瘤发展中的作用和对化疗效果的影响。方法:采用免疫组织化学、实时定量PCR 与Western blotting 比较人成骨细胞(human fetal osteoblasts,hFOB)和骨肉瘤(human OS,Saos2)细胞及人骨肉瘤细胞样本中 Wnt-beta-catenin信号通路相关分子的表达,比较hFOB和Saos2 细胞的表达差异。采用萤光素酶实验观察Wnt-beta-catenin、Notch、Hh 信号通路对氨甲喋呤(methotrexate,MTX)疗效的调控。结果:同hFOB细胞相比该通路的主要分子包括:Wnt3(5.5 倍)、beta-catenin (5.3 倍)、LEF1(7.6 倍),在Saos2细胞中表达明显上调。Western blotting 分析表明总beta-catenin 以及活化beta-catenin 的表达都升高。 MTX 处理后诱导了Saos2 细胞凋亡和坏死。对Wnt-beta-catenin、Notch、Hh 信号通路的化学抑制也能够诱导细胞死亡, Wnt-beta-catenin抑制剂更为明显。结论:采用小分子/ 化合物来抑制Wnt-茁-catenin 和Notch 信号,并同目前常用的OS药物化疗联 合使用,对于复发和转移的患者,有望改善患者的生存期。
英文摘要:
      Objective:To analyze the role ofWnt-beta-catenin signal pathway in the development of osteosarcoma and its effects on chemotherapy efficiency.Methods:Samples included human osteoblasts (hFOB) and osteosarcoma (Saos2) cells, and human osteosarcoma cells. By immunohistochemistry, real-time quantitative PCR and Western blotting, the Wnt-beta-catenin signaling pathway related molecules, expressions of hFOB and Saos2 cells were analyzed in all samples. Luciferase experiment was also applied to observe the regulation ofWnt-beta-catenin, Notch, Hh signal pathway on the therapeutic efficacy of MTX.Results:Compared with hFOB cells, the molecular pathways mainly included Wnt3 (5.5 times), beta-catenin (5.3 times), LEF1 (7.6 times), and expression was up-regulated in Saos2 cells. Western blotting analysis showed that the expression of total beta-catenin and activated beta-catenin were elevated. MTX treat- ment induced Saos2 cells apoptosis and necrosis. Chemistry inhibition on Wnt-beta-catenin, Notch, and Hh signaling pathway can also in- duce cell death, and Wnt-beta-catenin showed more obvious inhibition.Conclusion:Inhibition of Wnt-beta-catenin and Notch signals with small molecule/compounds and combined with the current commonly used chemotherapy of OS drugs, could improve the survival of relapse and metastasis patients.
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