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Effect of Apatinib Plus Melatonin on Vasculogenic Mimicry Formation by Cancer Stem Cells From Breast Cancer Cell Line Publisher Pubmed



Maroufi NF1, 2 ; Rashidi M3, 9 ; Vahedian V4 ; Jahanbazi R5 ; Mostafaei S6 ; Akbarzadeh M7 ; Kazemzadeh H8 ; Nejabati HR2 ; Isazadeh A8 ; Rashidi MR1 ; Nouri M1
Authors
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Authors Affiliations
  1. 1. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  4. 4. Researchers Club of Tums Preclinical Core Facility (TPCF), Tehran University of Medical Science (TUMS), Tehran, Iran
  5. 5. Department of Biology, Faculty of Science, Islamic Azad University, Falavarjan branch, Isfahan, Iran
  6. 6. Urmia University of Medical Sciences, Urmia, Iran
  7. 7. Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
  8. 8. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  9. 9. The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Source: Breast Cancer Published:2022


Abstract

Background and aim: Vasculogenic mimicry (VM) is one of the most important causes of breast cancer metastasis and resistance against drugs. The cancer stem cells (CSCs) are known as essential factors for VM formation. In this study, the effects of melatonin, Apatinib, and a combination of Apatinib/melatonin on VM formation were investigated by breast CSCs from breast cancer cell line. Materials and methods: The percentage of CSCs was determined in two breast cancer cell lines (MCF-7 and MDA-MB-231) by flow cytometry. The effects of Apatinib, melatonin, and a combination of Apatinib/melatonin were evaluated on proliferation and viability, migration and invasion, apoptosis, and VM formation in MDA-MB-231 cells. Moreover, expression levels of the involved proteins in cancer cell proliferation and viability, CSCs, migration and invasion, and VM formation were evaluated by real-time polymerase chain reaction (RT-PCR) and western blotting methods. Results: Results of the present study showed that melatonin and Apatinib reduced survival rate of CSCs in a dose- and time-dependent manner. Apatinib, melatonin, and a combination of Apatinib/melatonin inhibited proliferation of breast CSCs (P ≤ 0.001). Formation of VM was decreased in the MDA-MB-231 cancer cell line treated with Apatinib and combination of Apatinib/melatonin. Apatinib and combination of Apatinib/melatonin reduced invasion of breast CSCs (P ≤ 0.0001). Expression of vascular endothelial VE-cadherin, ephrinA2 receptor (EPHA2), p-PI3K/phosphoinositide-3 kinase (PI3K) and phospho-AKT (p-AKT)/AKT ratios was decreased under the influence of Apatinib and a combination of Apatinib/melatonin (P ≤ 0.01). Conclusion: Apatinib or a combination of Apatinib/melatonin may be used to manage patients with breast cancer. However, further studies are needed to identify anti-cancer mechanisms of melatonin and Apatinib for better management of the patients with breast cancer. © 2021, The Author(s), under exclusive licence to The Japanese Breast Cancer Society.