| 林 争,王 绎,明 华.Notch1信号通路调控乳腺癌肿瘤细胞放疗敏感性的机制研究[J].肿瘤学杂志,2018,24(7):687-691. |
| Notch1信号通路调控乳腺癌肿瘤细胞放疗敏感性的机制研究 |
| Effect of Notch1 Signaling Pathway on Regulating Radiosensitivity of Breast Cancer Cells and Its Mechanisms |
| 投稿时间：2017-11-01 |
| DOI：10.11735/j.issn.1671-170X.2018.07.B007 |
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| 中文关键词: 乳腺癌 Notch1信号通路 放疗敏感性 |
| 英文关键词:breast cancer Notch1 signaling pathway radiosensitivity |
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| 中文摘要: |
| 摘 要：［目的］ 探讨抑制Notch1信号通路对乳腺癌肿瘤细胞放疗敏感性的影响及机制。［方法］ Western blot检测人乳腺癌MCF-7细胞中加入5、10、20μmol/L的Notch1信号通路抑制剂γ分泌酶抑制剂(γ-secretase inhibitor，GSI)后Notch1、Hes1蛋白表达；克隆形成实验检测细胞经GSI和照射处理后增殖情况；后续实验分为对照组、GSI组和GSI+8Gy组，48h后CCK8实验检测细胞增殖；流式细胞仪检测细胞凋亡；Western blot检测Ki67、Cleaved caspase3蛋白表达。［结果］ 随着GSI的浓度增高，Notch1和Hes1蛋白表达随之降低(P<0.05)，且呈剂量依赖性关系。GSI与照射同时处理细胞较单纯用照射有较高的增敏比。GSI组和GSI+8Gy组细胞吸光值均显著性低于对照组(P<0.05)，而GSI+8Gy组吸光值显著性低于GSI组(P<0.05)，除对照组，GSI组和GSI+8Gy组随着处理时间的延长均明显降低(P<0.05)，呈时间依赖性关系。GSI组和GSI+8Gy组细胞凋亡率均显著性高于对照组，GSI+8Gy组细胞凋亡率显著性高于GSI组(P<0.01)。GSI组和GSI+8Gy组Ki67蛋白表达显著性低于对照组(P<0.05)，Cleaved caspase3蛋白表达显著性高于对照组(P<0.05)，GSI+8Gy组Ki67蛋白表达显著性低于GSI组，Cleaved caspase3蛋白表达显著性高于GSI组(P<0.05)。［结论］ 抑制Notch1信号通路可增强乳腺癌的放疗敏感性。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effect and mechanism of Notch1 signaling pathway on radiosensitivity of breast cancer cells. ［Methods］ Human breast cancer MCF-7 cells were treated with Notch1 signaling pathway γ-secretase inhibitor(GSI) 5，10，20μmol/L. The expressions of Notch1 and Hes1 protein were detected with Western blot，cell proliferation was detected by clone forming test. The MCF-7 cells were divided into the control group，GSI group and GSI+8Gy group. Cell proliferation was detected by CCK8 assay after 48h of treatment，cell apoptosis was detected by flow cytometry， the expression of Ki67 and cleaved Caspase3 protein was detected by Western blot.［Results］ With the increase of GSI concentration，the expression of Notch1 and Hes1 protein was decreased(P<0.05) in a dose-dependent manner. Compared with the irradiation，GSI and irradiation had a higher sensitivity enhancement ratio(SER). The absorbance in the GSI group and GSI+8Gy group were significantly lower than that in control group(P<0.05)，while the absorbance in the GSI+8Gy group was significantly lower than that in the GSI group(P<0.05). Except the control group，the absorbance in the GSI and GSI+8Gy group was increased in a time-dependent manner(P<0.05). The apoptosis rates of the GSI group and GSI+8Gy group were significantly higher than that of control group，and the apoptosis rate of the GSI+8Gy group was significantly higher than that of GSI group(P<0.05). The Ki67 protein expression in GSI group and GSI+8Gy group was significantly lower than that in control group(P<0.05)，the cleaved caspase 3 protein expression was significantly higher than that in control group(P<0.05). The Ki67 protein expression in the GSI+8Gy group than significantly lower than that in the GSI group，while the caspase3 protein expression was significantly higher than that in GSI group(P<0.05) . ［Conclusion］ Inhibition of Notch1 signaling pathway may increase radiosensitivity of breast cancer cells. |
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