紫铆因靶向EGFR和AuroraA/B信号通路抑制非小细胞肺癌的研究

Butein Inhibits Non-Small Cell Lung Cancer via Directly Targeting EGFR and AuroraA/B Signaling Pathways

紫铆因抗多种肿瘤的生物学活性已被广泛研究,但其抑制非小细胞肺癌(non-small cell lung cancer,NSCLC)的分子机制还不清楚。研究中,通过MTS和软琼脂集落实验检测紫铆因对非小细胞肺癌细胞停泊依赖和停泊非依赖增殖的影响,利用免疫印迹检测紫铆因处理后非小细胞肺癌表皮生长因子受体(epidermal growth factor receptor,EGFR)信号通路的磷酸化状态,同时采用流式细胞术检测紫铆因对非小细胞肺癌细胞周期演进的影响。研究发现紫铆因剂量依赖性抑制A549和H1650细胞增殖,在抑制EGFR信号通路磷酸化活化的同时下调EGFR总蛋白及EGFR在胞膜和胞核的表达,而且紫铆因下调AuroraA/B和H3-S10磷酸化,促进A549细胞G2/M期阻滞。结果表明紫铆因可通过靶向EGFR和AuroraA/B信号通路抑制非小细胞肺癌。

Antitumor activity of butein has been studied in various tumor types, but its potency in non-small cell lung cancer （NSCLC） is rarely known. Here, A549 and H1650 cells were treated with various concentra- tions of butein at different time points, the proliferation was evaluated by MTS and soft agar assay. What＇s more, the activation of EGFR signaling pathway after butein treatment was tested via immnnoblotting. Flow cytometry was conducted to assess cell cycle progression. The data showed that butein inhibited the prolifer- ation of A549 and H1650 cells in a dose-dependent manner. Butein treatment not only suppressed the phosphorylation of EGFR signaling pathway, but also resulted in down-regulation of total EGFR expression level, as well as EGFR expression on membrane and in nucleus. Additionally, the phosphorylation levels of AuroraA/B and H3-S10 were inhibited after butein exposure, and flow cytometry data demonstrated that butein induced G2/M cell cycle arrest. These data indicate that butein inhibits human NSCLC via directly targeting EGFR and AuroraA/B signaling pathways.