| Background and aim Vasculogenic mimicry (VM) is one of the most important causes of breast cancer metastasis and resist-
ance 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 prolif-
eration 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. |