FL118, a novel camptothecin analogue, suppressed migration and invasion of human breast cancer cells by inhibiting epithelial-mesenchymal transition <i>via</i> the Wnt/β-catenin signaling pathway
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- Yang Zhihong
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Ji Lixia
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Jiang Guohui
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Liu Ranran
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Liu Zhantao
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Yang Yuecheng
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Ma Qingxia
- Department of Pharmacology, School of Pharmacy, Qingdao University
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- Zhao Hongqin
- Department of Pharmacology, School of Pharmacy, Qingdao University
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説明
<p>The aim of the current study was to investigate the effects of FL118, a novel camptothecin analogue, on migration and invasion of human breast cancer cells and the underlying mechanisms of those effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a plate clone formation assay were used to examine inhibition of the proliferation of MDA-MB-231 cells by FL118. Cell cycle distribution was detected using flow cytometry. A wound healing assay and a transwell assay were performed to detect the effects of FL118 on migration and invasion of MDA-MB-231 cells, respectively. qRT-PCR, Western blotting, and immunocytochemistry were used to study the effects of FL118 on expression of epithelial-mesenchymal transition (EMT)-related molecules and Wnt/ β-catenin signaling components in MDA-MB-231 cells. The current results indicated that FL118 inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose- and time-dependent manner. FL118 caused MDA-MB-231 cells to accumulate in the S phase. FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin. Moreover, decreased expression of β-catenin and its targets survivin and cyclin Dl was detected in the nucleus of MDA-MB-231 cells. Taken together, the current results suggest that FL118 inhibited Wnt/β-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.</p>
収録刊行物
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- BioScience Trends
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BioScience Trends 12 (1), 40-46, 2018
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会