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

  • Authors:
    • Liang Xu
    • Le Zhang
    • Chun Hu
    • Shujing Liang
    • Xiaochun Fei
    • Ningning Yan
    • Yanyun Zhang
    • Fengchun Zhang
  • View Affiliations

  • Published online on: January 13, 2016     https://doi.org/10.3892/ijo.2016.3337
  • Pages:1175-1186
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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 including NANOG, SOX2 and OCT4, which were inherently upregulated in the BCSCs as compared with the bulk of cells within the tumor. Collectively, our findings provide direct evidence for PP serving as a promising high-yield agent targeting BCSCs and cancer heterogeneity. Therefore, strategies combining PP with standard chemotherapy drugs which fail to eliminate the BCSCs hold promise to overcome BCSCs associated treatment resistance and achieve a better therapeutic outcome.

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March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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Copy and paste a formatted citation
APA
Xu, L., Zhang, L., Hu, C., Liang, S., Fei, X., Yan, N. ... Zhang, F. (2016). WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. International Journal of Oncology, 48, 1175-1186. https://doi.org/10.3892/ijo.2016.3337
MLA
Xu, L., Zhang, L., Hu, C., Liang, S., Fei, X., Yan, N., Zhang, Y., Zhang, F."WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells". International Journal of Oncology 48.3 (2016): 1175-1186.
Chicago
Xu, L., Zhang, L., Hu, C., Liang, S., Fei, X., Yan, N., Zhang, Y., Zhang, F."WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells". International Journal of Oncology 48, no. 3 (2016): 1175-1186. https://doi.org/10.3892/ijo.2016.3337