Bauerane Induces 5-Phase Cell Cycle Arrest, Apoptosis, and Inhibition of Proliferation o f A549 Human Lung Cancer Cells Through the Phosphoinositide 3-Kinase (PI3K)/AKT and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway
Bauerane Induces 5-Phase Cell Cycle Arrest, Apoptosis, and Inhibition of Proliferation o f A549 Human Lung Cancer Cells Through the Phosphoinositide 3-Kinase (PI3K)/AKT and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway
复制标题
DOI：
10.12659/msm.919558
复制
发表时间：
2020-02-01
影响因子：
3.1
通讯作者：
Shen, Chengji
中科院分区：
文献类型：
--
作者：
Chen, Qin;Wang, Ming;Shen, Chengji
背景：蒲公英醚是从蒲公英根（Taraxacum officinale）中提取的三萜化合物。本研究旨在探讨鲍威烷对人肺癌A549细胞增殖的影响及其分子机制。材料/方法：培养A549人肺腺癌细胞和正常的MRC-5肺成纤维细胞，并在0、2.5、5、10、20、40、80和160 μ m的环境下，用增加剂量的bauerane处理。4′，6-二氨基-2-苯基吲哚（DAPI）和吖啶橙/溴化乙啶（AO/EB）染色评估细胞凋亡。流式细胞术测定细胞周期。Western blot检测细胞色素c、Bax、cyclin 81、Bcl-2、PI3K、p-PI3K、Akt、p-Akt和STAT3蛋白的表达水平。结果：Bauerane抑制A549肺癌细胞增殖呈剂量依赖性，IC50为10 μ M，对MRC-5细胞无细胞毒性。Bauerane处理诱导A549细胞凋亡，与Bax上调、Bcl-2下调有关。Bauerane诱导A549细胞的s期阻滞，这是剂量依赖性的，并且与cyclin B1的表达降低有关。Western blot结果显示，bauerane抑制了PI3K/AKT和STAT3信号通路的磷酸化。结论：Bauerane体外抑制A549肺癌细胞增殖，诱导细胞凋亡和细胞周期阻滞呈剂量依赖性。
Background: Bauerane is a triterpenoid derived from the dandelion root (Taraxacum officinale). This study aimed to investigate the effects of bauerane on cell proliferation of A549 human lung cancer cells and the molecular mechanisms involved.Material/Methods: A549 human lung adenocarcinoma cells and normal MRC-5 lung fibroblasts were grown in culture and treated with increasing doses of bauerane at 0, 2.5, 5, 10, 20, 40, 80, and 160 mu M. The MIT assay was used to measure cell proliferation. Cell apoptosis was assessed by 4', 6-diamidino-2-phenylindole (DAPI), and acridine orange/ethidium bromide (AO/EB) staining. The cell cycle was evaluated by flow cytometry. Western blot measured the protein expression levels of cytochrome c, Bax, cyclin 81, Bcl-2, PI3K, p-PI3K, Akt, p-Akt, and STAT3 proteins.Results: Bauerane inhibited the proliferation of A549 lung cancer cells in a dose-dependent manner, with an IC50 of 10 mu M, with no cytotoxicity for MRC-5 cells. Bauerane treatment induced apoptosis of A549 cells, which was associated with the upregulation of Bax and down-regulation of Bcl-2. Bauerane induced S-phase arrest of A549 cells, which was dose-dependent and associated with reduced expression of cyclin B1. The findings from Western blot showed that bauerane inhibited the phosphorylation of PI3K/AKT and STAT3 signaling pathways.Conclusions: Bauerane inhibited the proliferation of A549 lung cancer cells in vitro and induced cell apoptosis and cell cycle arrest in a dose-dependent manner.