Nazila Fathi Maroufi1,2, Mohsen Rashidi3,4, Vahid Vahedian5, Raheleh Jahanbazi6, Sahar Mostafaei7, Maryam Akbarzadeh8, Hamid Kazemzadeh9, Hamid-Reza Nejabati2, Alireza Isazadeh9, Mohammad-Reza Rashidi10, Mohammad Nouri11. 1. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 4. The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 5. Researchers Club of Tums Preclinical Core Facility (TPCF), Tehran University of Medical Science (TUMS), Tehran, Iran. 6. Department of Biology, Faculty of Science, Islamic Azad University, Falavarjan branch, Isfahan, Iran. 7. Urmia University of Medical Sciences, Urmia, Iran. 8. Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands. 9. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 10. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. Rashidi@tbzmed.ac.ir. 11. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. nourimd@yahoo.com.
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.
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.
Authors: Lei Wang; Zeng Jin; Rohan P Master; Chandra K Maharjan; Madison E Carelock; Tiffany B A Reccoppa; Myung-Chul Kim; Ryan Kolb; Weizhou Zhang Journal: Cancers (Basel) Date: 2022-07-05 Impact factor: 6.575