紫杉醇联合顺铂调控NOD1、NF-κB、R1P2信号治疗乳腺癌的机制研究

Mechanism of Paclitaxel Combined with Cisplatin Regulating NOD1,NF-κB and R1P2 Signal in the Treatment of Breast Cancer

目的研究紫杉醇联合顺铂调控NOD1、NF-κB、R1P2信号通路在乳腺癌细胞FASN高表达中的作用。方法对人乳腺癌细胞系(SK-BR-3、MCF-7和MDA-MB-231)分别给予紫杉醇联合顺铂治疗(实验组)与顺铂治疗(对照组)进行处理,随后采用流式细胞仪和Western blot法对细胞的细胞周期和通路蛋白表达水平进行检测。结果在实验组中,随药物浓度增加,休眠细胞暂不分裂期～第一个生长期(G_0～G_1)、DNA合成期(S期)细胞逐渐减少,DNA合成后期～有丝分裂期(G_2～M期)细胞明显增多,呈剂量-效应趋势;实验组乳腺癌细胞阻断在G_0、G_1期;随浓度增加,S期有所延长,G_2、M期缩短;对照组的实验结果与实验组实验结论一样,但效果没有紫杉醇联合顺铂组明显;实验组乳腺癌细胞SK-BR-3、MCF-7和MDA-MB-231细胞系中NOD1、NF-κB、R1P2信号通路中脂肪酸合酶FASN表达较对照组显著下降。结论紫杉醇联合顺铂治疗通过调控NOD1、NF-κB、R1P2信号通路参与乳腺癌细胞FASN的表达,使其表达量下降,为乳腺癌的控制和治疗提供新的思路和方法。

Objective To study that Paclitaxel combined with Cisplatin therapy for regulating NOD1,NF-κB and R1P2 signaling pathway in breast cancer cells with high FASN expression.Methods The human breast cancer cell lines(SK-BR-3,MCF-7 and MDA-MB-231)were treated with Paclitaxel plus Cisplatin(the experimental group)or Cisplatin alone(the control group),followed by the flow cytometry and western blot assay and the cell cycle pathway protein levels were detected.Results In the experimental group,with the increase of the drug concentration,in G 0-G 1 and S phase,the number of cells decreased,while for G 2-M phase,cells increased in a dose dependent manner.The experimental group of breast cancer cells were blocked in G 0/G 1 phase.With increasing concentration of the treatment,the length of S phase increased,while G 2/M was shortened.The control group had the similar results as the experimental group,but not as significant;The fatty acid synthase(FASN)expression in NOD1,NF-κB and R1P2 signaling pathways for all three breast cancer cell lines of the experimental group was significantly lower than that of the control group.Conclusion Paclitaxel combined with Cisplatin therapy is decreasing the expression of FASN in breast cancer cells by regulating NOD1,NF-κB and R1P2 signaling pathways,,which providing a novel approach for the control and treatment of breast cancer.