顺铂通过Notch1下调CXCR4对乳腺癌细胞增殖能力的影响

The effect of cisplatin on breast cancer cell proliferation by down-regulating CXCR4 through Notch1 pathway

目的从细胞水平上探讨顺铂(DDP)对乳腺癌MDA-MB-231细胞系增殖的影响,以及其可能机制。方法使用不同浓度(0、1.25、2.5、5、10、20、40μmol/L)的顺铂作用于乳腺癌细胞系MDA-MB-231;CCK-8方法检测各浓度组细胞24h后的增殖情况;选取对细胞增殖影响显著的顺铂浓度(0、10、20、40μmol/L)作用MDA-MB-231细胞24h,收集细胞并采用Western blot方法检测CXCR4的表达;采用Notch1抑制剂MK0752预处理MDA-MB-231细胞2h后,再用浓度为20μmol/L的顺铂作用于预处理的MDA-MB-231细胞24h后收集细胞,并采用Western blot方法检测阻断效果以及CXCR4的表达。结果顺铂可以抑制乳腺癌细胞的增殖(P<0.05);与对照组相比,随着浓度给药浓度的增加,CXCR4的表达显著降低(P<0.05);阻断Notch1(阻断组)后,与未阻断组(Notch1未被阻断)相比,CXCR4的表达显著降低(P<0.001)。结论化疗药物顺铂部分通过Notch1抑制CXCR4的表达,从而抑制乳腺癌细胞增殖。

Objective At the cellular level,to explored the effect of cisplatin(DDP)on the proliferation of breast cancer MDA-MB-231 cell line and its possible mechanism.Methods Using different concentrations(0,1.25,2.5,5,10,20,40μmol/L)of cisplatin on breast cancer cell line MDA-MB-231;CCK-8 method was used to detect the proliferation of cells in each concentration group after 24 h.Selected the cisplatin concentration(0,10,20,40μmol/L)that has a significant effect on cell proliferation to act on MDA-MB-231 cells for 24 h,collected the cells and detected the expression of CXCR4 by Western blot.Pre-treated MDA-MB-231cells with Notch1 inhibitor MK0752 for 2 h,then the pretreated MDA-MB-231 cells were treated with cisplatin at a concentration of 20μmol/L for 24 h,and the cells were collected to detect the blocking effect and the expression of CXCR4 by Western blot.Results Cisplatin could inhibit the proliferation of breast cancer cells(P<0.05).Compared with the control group,the expression of CXCR4 was significantly reduced with the increase of the concentration of the administration(P<0.05).After blocking Notch1(blocking group),compared with the unblocked group(Notch1 was not blocked),the expression of CXCR4 was significantly reduced(P<0.001).Conclusion The chemotherapeutic drug cisplatin partially inhibits the expression of CXCR4 through Notch1,thereby inhibiting breast cancer cell proliferation.