| 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].,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 |
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| 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) |
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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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