Alfoudiry Mariam M, Khajah Maitham A
Department of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Biomedicines. 2025 Feb 24;13(3):567. doi: 10.3390/biomedicines13030567.
Endocrine resistance in breast cancer is associated with the epithelial-to-mesenchymal transition (EMT), resulting in enhanced cell proliferation, motility, and invasion and leading to a poor prognosis. There are few studies regarding the role of Angiotensin II (Ang II) and Angiotensin 1-7 (Ang 1-7) in relation to breast cancer, with contradictory outcomes. This study aims to investigate the expression of Ang 1-7 and MAS-R and evaluate the effects of Ang II, Ang 1-7, and the MAS-R agonist AVE0991 on EMT induction and reversal. The effects of Ang II and Ang 1-7 on normal and breast cancer cell lines were determined using various techniques for cell proliferation (MTT), motility (scratch assay), and invasion (Cultrex assay). Also, the expression/localization profiles of Ang 1-7 and its receptor (MAS-R), as well as various EMT markers, were determined using immunofluorescence, western blot, and ELISA. Ang II significantly decreased the motility of the tested cell lines; however, it did not have a significant effect on their proliferation or invasion. The expression profiles of the tested EMT markers were not affected by Ang II treatment. The expression levels of Ang 1-7 and MAS-R were significantly higher in the normal breast epithelial cells and estrogen receptor ER compared to the ER+ breast cancer cells. Treatment with Ang 1-7 or the non-peptide MAS-R agonist AVE0991 significantly reduced the migration and invasion of the tested cell lines without modulating the tested EMT markers. Compared to Ang 1-7, AVE0991 exhibited a more prominent dose-dependent inhibitory effect on the proliferation, motility, and invasion of the ER- breast cancer cells. Ang 1-7 and AVE0991 play a promising therapeutic role in breast cancer, in part by reducing cell motility and invasion.
乳腺癌中的内分泌抵抗与上皮-间质转化（EMT）相关，导致细胞增殖、运动和侵袭增强，并导致预后不良。关于血管紧张素II（Ang II）和血管紧张素1-7（Ang 1-7）在乳腺癌中的作用的研究很少，结果相互矛盾。本研究旨在研究Ang 1-7和MAS-R的表达，并评估Ang II、Ang 1-7和MAS-R激动剂AVE0991对EMT诱导和逆转的影响。使用各种细胞增殖（MTT）、运动（划痕试验）和侵袭（Cultrex试验）技术测定Ang II和Ang 1-7对正常和乳腺癌细胞系的影响。此外，使用免疫荧光、蛋白质免疫印迹和酶联免疫吸附测定法测定Ang 1-7及其受体（MAS-R）以及各种EMT标志物的表达/定位谱。Ang II显著降低了受试细胞系的运动能力；然而，它对它们的增殖或侵袭没有显著影响。受试EMT标志物的表达谱不受Ang II处理的影响。与ER+乳腺癌细胞相比，正常乳腺上皮细胞和雌激素受体ER中Ang 1-7和MAS-R的表达水平显著更高。用Ang 1-7或非肽类MAS-R激动剂AVE0991处理可显著降低受试细胞系的迁移和侵袭，而不调节受试的EMT标志物。与Ang 1-7相比，AVE0991对ER-乳腺癌细胞的增殖、运动和侵袭表现出更显著的剂量依赖性抑制作用。Ang 1-7和AVE0991在乳腺癌中发挥着有前景的治疗作用，部分原因是它们降低了细胞的运动和侵袭能力。
