The effect of vandetanib and thymoquinone on the molecular indicators of vascologenic mimicry by cancer stem cells from breast cancer cell line

Abstract

Vasculogenic mimicry is characterized by the formation of tubular structur through cancer stem cells inside the tumor stroma wicth leading to enhanced metastasis to the remote sites. Methods: MDA-MB-231 CSCs were incubated with different concentrations of TQ and vandetanib for 48 hours. The viability of CSCs was determined using the MTT assay. By using the Matrigel assay, we measured the tubulogenesis capacity. The percent of CSCs and Rhodamine 123 efflux capacity was studied using flow cytometry analysis. Protein levels of Akt, p-Akt, Wnt3a, VE-cadherin, MMP-2 and MMP-9 were detected by western blotting. Results: TQ and vandetanib decreased the viability of CSCs in a dose-dependent manner. TQ and vandetanib could blunt the stimulatory effect of VEGF, EGF, FGF on CSCs (p<0.05). The vasculogenic capacity of CSCs was reduced after being-exposed to TQ and vandetanib (p<0.05). TQ and vandetanib decreased the protein levels of VE-cadherin, MMP-2, MMP-9, p-Akt/Akt and Wnt3a. TQ and vandetanib had the potential to decrease the number of CD24- /CD44+ CSCs and Rhodamine 123 efflux capacity after 48 hours.