The Effect of Melatonin and Apatinib on the Vascologenic Mimicry by Cancer Stem Cells from Breast Cancer Cell Line

Abstract

The vasculogenic mimicry (VM) is one of the most important causes of breast cancer metastasis and drug resistance. In this study, the effects of melatonin and apatinib on the formation of VM by breast cancer stem cells were investigated. Methods: The effects of apatinib, melatonin and melatonin / apatinib combination on proliferation, viability and formation of VM in MDA-MB-231 stem cells were investigated. In addition, the expression levels of proteins involved in the proliferation, survival of cancer cells and VM formation were examined by Real-Time and Western blotting. Results: Melatonin and apatinib reduced the survival rate of cancer stem cells dose and time dependent manner. Apatinib, melatonin and apatinib / melatonin combination inhibited the proliferation of breast cancer stem cells (P≤0.001). The formation of VM decreased in the MDA-MB-231 cancer cell line treated with apatinib and apatinib / melatonin (P≤0.01). Apatinib and apatinib / melatonin reduced the invasion of breast cancer stem cells (P≤ 0.0001). VE-cadherin, EPHA2 expression and p-PI3K / PI3K and p-AKT / AKT ratios decreased under the treatment of apatinib and apatinib / melatonin (P≤0.01).