ADAM10抑制剂GI254023X对乳腺癌细胞体外生物学行为的影响及机制

发布时间：2018-05-03 08:13

本文选题：去整合素金属蛋白酶 + 乳腺肿瘤　；参考：《山东医药》2017年38期

【摘要】：目的观察高选择性去整合素金属蛋白酶10(ADAM10)抑制剂GI254023X对乳腺癌细胞株MCF-7、MDA-MB-231增殖、凋亡、侵袭、迁移等生物学行为的影响,并初步探讨其可能作用机制。方法取乳腺癌细胞株MCF-7、MDA-MB-231,用不同浓度(0、10、20、30、40、50μmol/L)的GI254023X分别处理两种细胞48、72 h,采用CCK-8检测细胞增殖能力。取MCF-7、MDA-MB-231细胞,将其分为对照组、低浓度组与高浓度组,低浓度组加入10μmol/L的GI254023X,高浓度组加入20μmol/L的GI254023X,对照组加入和实验组等量的DMSO溶剂,采用流式细胞仪测算细胞凋亡率,Transwell实验检测细胞迁移侵袭能力,Western boltting法检测切割后的Notch1(CleavedNotch1)、Hes-1蛋白表达,qRT-PCR法检测细胞Hes-1 mRNA表达。结果随着GI254023X药物浓度增加及作用时间的延长,MCF-7、MDA-MB-231细胞增殖抑制率不断升高(P均0.05)。与对照组相比,低浓度组、高浓度组MCF-7、MDA-MB-231细胞凋亡率高,迁移细胞数、侵袭细胞数少,Cleaved-Notch1、Hes-1蛋白表达少,Hes-1 mRNA表达少,且高浓度组较低浓度组更明显(P均0.05)。结论 ADAM10抑制剂GI254023X可抑制乳腺癌细胞株MCF-7、MDA-MB-231增殖,诱导其凋亡,减弱其迁移和侵袭运动能力,该作用可能是通过下调ADAM10的表达来抑制Notch1信号通路的活化实现的。
[Abstract]:Objective to investigate the effects of high selective deintegrin metalloproteinase-10 (ADAM10) inhibitor GI254023X on the proliferation, apoptosis, invasion and migration of breast cancer cell line MCF-7MDA-MB-231, and to explore its possible mechanism. Methods Breast cancer cell line MCF-7 MDA-MB-231 was treated with GI254023X of different concentrations of 10, 10, 20, 30 and 4050 渭 mol / L respectively for 4872 hours, and the proliferative ability of the two cells was measured by CCK-8. MCF-7 MDA-MB-231 cells were divided into control group, low concentration group and high concentration group. The low concentration group added 10 渭 mol/L GI254023X. the high concentration group added 20 渭 mol/L GI254023X. the control group added the same amount of DMSO solvent as the experimental group. Cell apoptosis rate was measured by flow cytometry and transwell assay was used to detect the ability of cell migration and invasion. Western boltting assay was used to detect the expression of Notch1CleavedNotch1Hes-1 protein. QRT-PCR was used to detect the expression of Hes-1 mRNA. Results with the increase of GI254023X concentration and the prolongation of the time of treatment, the proliferation inhibition rate of MCF-7 MDA-MB-231 cells increased continuously (P < 0.05). Compared with the control group, the apoptosis rate of MDA-MB-231 cells was higher, the number of migration cells, the number of invasive cells and the expression of Hes-1 protein of Cleaved-Notch1 Hes-1 protein were lower in the low concentration group than in the control group, and the expression of Hes-1 mRNA in the high concentration group was more obvious than that in the low concentration group. Conclusion ADAM10 inhibitor GI254023X can inhibit the proliferation, induce apoptosis and decrease the migration and invasion of breast cancer cell line MCF-7 MDA-MB-231. This effect may be achieved by down-regulating the expression of ADAM10 to inhibit the activation of Notch1 signaling pathway.
【作者单位】：泰山医学院附属医院;泰安市中心医院;徐州医科大学附属医院;
【基金】：江苏省“六大人才高峰”B类项目(2014-WSW-040)
【分类号】：R737.9

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