Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, U.S.A.
Cancer Genomics Proteomics. 2022 Jan-Feb;19(1):19-26. doi: 10.21873/cgp.20300.
BACKGROUND/AIM: The aberrant regulation of erythropoietin-producing hepatocellular carcinoma (EPH) receptors and ephrin ligands has been implicated in breast carcinoma, and artesunate has been shown to have anticancer effects. The aim of this study was to characterize the involvement of EPH receptors and ephrin ligands in mediating artesunate (ART)-induced growth suppression of normal breast cells and breast carcinoma cell lines.
The normal breast epithelial cells (MCF10A), non-invasive ductal breast carcinoma cells (MCF7), and invasive triple-negative breast carcinoma cells (MDA-MB-231) were grown in the absence or the presence of different concentrations of artesunate. The cells were counted, and total RNA was isolated. The abundance of transcripts corresponding to EPH receptors and ephrin ligands was determined by quantitative polymerase chain reaction.
Cell viability was significantly reduced when cells were treated with artesunate, with MDA-MB-231 cells having the highest sensitivity. Artesunate had no significant effect on transcription of EPH/ephrins in MCF10A cells, but markedly increased EPHA8, EPHA10, EPHB6 and ephrin-A2 expression in MCF7 cells, and significantly increased EPHA3 and EPHA10 expression while reducing that of EPHA7 and ephrin-A3 in MDA-MB-231 cells.
The relative changes in artesunate-treated MCF7 and MDA-MB-231 cells as compared to similarly treated MCF10A cells allow us to implicate combinatorial expression and receptor interactions for EPH receptor-mediated signal transduction that converges into pathways responsible for cell growth, proliferation, and apoptosis. Specifically, the alterations in EPHA7, EPHA8, EPHA10 and EPHB6 transcripts appear to be important participants in artesunate-mediated cellular effects.
背景/目的：促红细胞生成素产生肝细胞癌 (EPH) 受体和 EPH 配体的异常调节与乳腺癌有关，青蒿琥酯已显示出抗癌作用。本研究旨在探讨 EPH 受体和 EPH 配体在介导青蒿琥酯 (ART) 抑制正常乳腺细胞和乳腺癌细胞系生长中的作用。
在不存在或存在不同浓度青蒿琥酯的情况下，培养正常乳腺上皮细胞 (MCF10A)、非侵袭性乳腺导管癌细胞 (MCF7) 和侵袭性三阴性乳腺癌细胞 (MDA-MB-231)。细胞计数后分离总 RNA。通过定量聚合酶链反应测定对应于 EPH 受体和 EPH 配体的转录物的丰度。
细胞用青蒿琥酯处理后，细胞活力显著降低，其中 MDA-MB-231 细胞的敏感性最高。青蒿琥酯对 MCF10A 细胞中 EPH/ephrin 的转录没有显著影响，但显著增加了 MCF7 细胞中 EPHA8、EPHA10、EPHB6 和 ephrin-A2 的表达，同时降低了 MDA-MB-231 细胞中 EPHA7 和 ephrin-A3 的表达。
与同样处理的 MCF10A 细胞相比，青蒿琥酯处理的 MCF7 和 MDA-MB-231 细胞的相对变化表明，EPH 受体介导的信号转导的组合表达和受体相互作用对于细胞生长、增殖和凋亡负责的途径至关重要。具体来说，EPHA7、EPHA8、EPHA10 和 EPHB6 转录本的改变似乎是青蒿琥酯介导的细胞效应的重要参与者。
