WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells

International Journal of Oncology
Liang XuFengchun Zhang

Abstract

Acquisition of chemoresistance and metastatic phenotype are the major causes of breast cancer treatment failure and cancer-related mortality. Recently, a plethora of experimental and clinical studies points toward a central role of cancer stem cells (CSCs) in the chemoresistance and metastasis. In the present study, we demonstrated that pyrvinium pamoate (PP), an anthelmintic drug, inhibited proliferation of different subtypes of breast cancer cells (luminal: MCF-7, claudin-low: MDA-MB‑231, basal-like: MDA-MB‑468 and Her-2 enriched: SkBr-3) as a novel WNT pathway inhibitor. Additionally, PP was also shown to inhibit self-renewal of breast cancer stem cells (BCSCs) and decrease both CD44+CD24-/low and ALDH-positive BCSCs content in a panel of breast cancer cell lines. Besides, the metastatic potential and expression of EMT markers (such as N-cadherin, vimentin, Snail) were also found suppressed by PP. By using a xenograft model, we next tested the efficacy of PP on tumorigenicity of MDA-MB‑231, one of the most aggressive breast cancer cell lines, and we observed PP significantly delayed tumor growth in vivo. Moreover, in-depth analysis revealed that PP caused inhibition of WNT pathway activity and stemness regulator expression i...Continue Reading

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