The Enzalutamide and EPI-001 modulate cell proliferation and metastasis markers in T47D by targeting AR/ARV7

IF 0.7 Q4 PHARMACOLOGY & PHARMACY
Belal M Ali, Hanan S El-Abhar, Dalaal M Abdallah, Ghada Mohamed, Marwa Sharaky, Samia A. Shouman, Marwa Kamel
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引用次数: 0

Abstract

Androgen receptor (AR) and its splicing variant 7 (ARv7) play vital roles in the pathobiology of breast cancer (BC) but their role in the estrogen receptor-positive (ER+) type is controversial. Hence, we studied the influence of the blockers of AR (Enzalutamide) and ARv7 (EPI-001) on tumorigenesis processes using T47D, an ER+ BC cell line. Several techniques were employed: Sulphorhodamine assay (SRB), Flow cytometry, Immunostaining, Scratch wound healing assay, Enzyme Linked Immunosorbent assay (ELISA), and Western blot. Mechanistically, the drugs successfully arrested the cell cycle at S-phase and downregulated the protein expression of cyclins A, E, & C. Additionally, they inhibited the cell proliferation stimulator nuclear factor kappa B (NF-ĸB), whereas only EPI-001 reduced the cell regulatory marker c-Myc. They also opposed the endothelial-to-mesenchymal transition (EMT) process, by boosting the epithelial marker E-cadherin and reducing the protein expression of the mesenchymal marker fibronectin. Their anti-metastatic potential was evidenced by the hindrance of cell migration using the wound healing assay and further confirmed by the downregulation of metalloproteinase (MMP) 2 and 9 protein expression, and protein content of Rho kinase (ROCK)1 and 2. Besides, by downregulating the protein expression of vascular endothelial growth factor (VEGF) the drugs point to their anti-angiogenic aptitude. In conclusion, this in-vitro study highlights the importance of targeting AR/ARv7 using Enzalutamide and EPI-001 in decreasing proliferation cell markers, EMT, and metastasis in ER+ BC cells, findings that may have great impact in the treatment of ER+ BC.
Enzalutamide和EPI-001通过靶向AR/ARV7调节T47D细胞增殖和转移标志物
雄激素受体(AR)及其剪接变体7 (ARv7)在乳腺癌(BC)的病理生物学中起着重要作用,但它们在雌激素受体阳性(ER+)型中的作用尚存争议。因此,我们利用ER+ BC细胞系T47D研究了AR阻断剂(Enzalutamide)和ARv7阻断剂(EPI-001)对肿瘤发生过程的影响。采用了几种技术:硫罗丹明试验(SRB)、流式细胞术、免疫染色、划伤愈合试验、酶联免疫吸附试验(ELISA)和Western blot。从机制上讲,这些药物成功地阻止了细胞周期在s期,并下调了细胞周期蛋白A、E和amp的蛋白表达;C.此外,它们抑制细胞增殖刺激因子核因子κ B (NF-ĸB),而只有EPI-001降低细胞调节标志物c-Myc。他们还通过提高上皮标记物e -钙粘蛋白和降低间充质标记物纤维连接蛋白的表达来反对内皮到间充质转化(EMT)过程。通过伤口愈合实验证明了它们的抗转移潜力,并通过下调金属蛋白酶(MMP) 2和9蛋白表达以及Rho激酶(ROCK)1和2蛋白含量进一步证实了它们的抗转移潜力。此外,通过下调血管内皮生长因子(VEGF)的蛋白表达,表明药物具有抗血管生成的能力。总之,这项体外研究强调了使用Enzalutamide和EPI-001靶向AR/ARv7在降低ER+ BC细胞增殖细胞标志物、EMT和转移中的重要性,这些发现可能对ER+ BC的治疗有很大影响。
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来源期刊
INDONESIAN JOURNAL OF PHARMACY
INDONESIAN JOURNAL OF PHARMACY PHARMACOLOGY & PHARMACY-
CiteScore
1.20
自引率
0.00%
发文量
38
审稿时长
12 weeks
期刊介绍: The journal had been established in 1972, and online publication was begun in 2008. Since 2012, the journal has been published in English by Faculty of Pharmacy Universitas Gadjah Mada (UGM) Yogyakarta Indonesia in collaboration with IAI (Ikatan Apoteker Indonesia or Indonesian Pharmacist Association) and only receives manuscripts in English. Indonesian Journal of Pharmacy is Accredited by Directorate General of Higher Education. The journal includes various fields of pharmaceuticals sciences such as: -Pharmacology and Toxicology -Pharmacokinetics -Community and Clinical Pharmacy -Pharmaceutical Chemistry -Pharmaceutical Biology -Pharmaceutics -Pharmaceutical Technology -Biopharmaceutics -Pharmaceutical Microbiology and Biotechnology -Alternative medicines.
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