| 孙晓江,徐 超,姚庆华.姜黄素对结肠癌氟尿嘧啶耐药细胞株中NKD2和TET1的调控作用[J].肿瘤学杂志,2016,22(11):928-933. |
| 姜黄素对结肠癌氟尿嘧啶耐药细胞株中NKD2和TET1的调控作用 |
| Role of Curcumin in Up-regulation of NKD2 and TET1 in 5-Fu Resistant Colon Cancer Cells |
| 投稿时间：2016-10-12 |
| DOI：10.11735/j.issn.1671-170X.2016.11.B012 |
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| 中文关键词: 姜黄素 5-Fu耐药细胞株(5FUR) NKD2 TET1 Caspase-3 |
| 英文关键词:curcumin 5-Fu resistant colon cancer cells(5FUR) NKD2 TET1 Caspase-3 |
| 基金项目:国家自然科学基金项目（81673813） |
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| 摘要点击次数: 1466 |
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| 中文摘要: |
| 摘 要：［目的］ 通过体外实验观察姜黄素对5-Fu耐药细胞株（5FUR）中NKD2、TET1及Caspase-3表达水平的影响。［方法］ 运用Western blot、Real-time qPCR检测不同浓度姜黄素对5FUR细胞及转染TET1 shRNA后5FUR细胞内NKD2、Caspase-3蛋白和mRNA表达的影响。通过重亚硫酸测序（BSP）的方法，观察姜黄素对NKD2基因启动子去甲基化的干预情况。［结果］ 经过5-Fu培养而得到5FUR的 IC50为（86.91±3.61）μg/ml（P<0.001）。HCT-116原代细胞5-Fu的IC50为(12.64±1.52) μg/ml，姜黄素对其增殖的抑制率为38.34%（P<0.001），姜黄素能显著上调5FUR细胞内NKD2、TET1的表达，且呈剂量依赖性。TET1转染敲低后检测发现5FUR细胞中的NKD2及Caspase-3的表达受到明显的抑制。［结论］ 姜黄素能从体外明显抑制结肠癌细胞5FUR的生长，其作用机制可能通过去甲基化调控蛋白TET1促使抑制基因NKD2基因启动子发生去甲基化，从而上调NKD2的表达，最终起到抑制肿瘤生长的作用。 |
| 英文摘要: |
| Abstract：［Objective］ To observe the effects of curcumin on the expression of NKD2，TET1 and Caspase-3 in 5FUR cells. ［Methods］ The protein and mRNA expression of NKD2，TET1 and Caspase-3 in the 5FUR cells treated with different concentrations of curcuminwere tested by Western blot and Real-time qPCR.The methylation in the promotor of 5FUR treated with different concentrations of curcumin was tested by Bisulfite sequencing PCR. ［Results］The IC50 of 5FUR cells treated by 5-Fu reach（86.91±3.61）μg/ml（P<0.001），while the HCT-116 cells reach（12.64±1.52）μg/ml.Curcumin triggered massive proliferation in these malignant cells (ratio of 38.34%，P<0.001).Curcumin can upregulate the expression of NKD2，TET1 in a dose-dependent manner in 5FUR cells. When knocking down the TET1，the expression level of NKD2 and Caspase-3 in 5FUR cells was inhibited.Curcumin can reverse this progress. ［Conclusion］ Curcumin can significantly inhibit the growth of 5FUR cells in vivo.Curcumin may upregulate the expression of TET1 which may demathylate the promotor of NKD2 to enhance the expression and inhibit tumor invasion and metastasis eventually. |
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