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Breast Cancer
Published in: Breast Cancer 2/2022

01-03-2022 | Breast Cancer | Original Article

Effect of Apatinib plus melatonin on vasculogenic mimicry formation by cancer stem cells from breast cancer cell line

Authors: Nazila Fathi Maroufi, Mohsen Rashidi, Vahid Vahedian, Raheleh Jahanbazi, Sahar Mostafaei, Maryam Akbarzadeh, Hamid Kazemzadeh, Hamid-Reza Nejabati, Alireza Isazadeh, Mohammad-Reza Rashidi, Mohammad Nouri

Published in: Breast Cancer | Issue 2/2022

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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.
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Metadata
Title
Effect of Apatinib plus melatonin on vasculogenic mimicry formation by cancer stem cells from breast cancer cell line
Authors
Nazila Fathi Maroufi
Mohsen Rashidi
Vahid Vahedian
Raheleh Jahanbazi
Sahar Mostafaei
Maryam Akbarzadeh
Hamid Kazemzadeh
Hamid-Reza Nejabati
Alireza Isazadeh
Mohammad-Reza Rashidi
Mohammad Nouri
Publication date
01-03-2022
Publisher
Springer Singapore
Published in
Breast Cancer / Issue 2/2022
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-021-01310-4

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