HMQ-T-F5 (1-(4-(2-aminoquinazolin-7-yl)phenyl)-3-(2‑bromo‑5- (trifluoromethoxy)phenyl) thiourea) suppress proliferation and migration of human cervical HeLa cells via inhibiting Wnt/β-catenin signaling pathway

Abstract

BackgroundDrug therapy plays an important role in the treatment of cervical cancer, which is one of the most common solid tumors in women. Therefore, it is important to seek more effective and less toxic therapies. PurposeThe aim of this study is to investigate the therapeutic potential of HMQ-T-F5 (1-(4-(2-aminoquinazolin-7-yl)phenyl)-3-(2‑bromo‑5-(trifluoromethoxy) phenyl)thiourea) (F5) for cervical cancer and explore the related mechanism. MethodsBy performing MTT assay, colony formation assay, flow cytometry, wound-healing assay, transwell assay, immunofluorescent staining and siRNA assay, we study the effect of F5 on human cervical HeLa cells. The mechanism of F5 was also investigated. ResultsWe found that F5 significantly inhibited HeLa cell proliferation, led to accumulation of cells in the S phase, and induced apoptosis and inhibited migration. Mechanistically, F5 inhibited HeLa cell growth and migration through repressing the expression and nuclear translocation of β-catenin, enhancing Axin expression, inhibiting the phosphorylation of LRP5/6 and GSK3β, as well as downregulating the Wnt downstream targeted proteins. Knockdown of a checkpoint β-catenin by siRNA significantly attenuated HeLa cell proliferation. Furthermore, XAV939, an inhibitor of β-catenin, was used to treat HeLa cells and the results demonstrated that F5 inhibited proliferation and migration via the inhibition of the Wnt/β-catenin pathway. ConclusionOur findings demonstrated that F5 can target β-catenin potentially and is useful in the treatment of cervical cancer.