Open Access

Niclosamide inhibits the cell proliferation and enhances the responsiveness of esophageal cancer cells to chemotherapeutic agents

  • Authors:
    • Ming‑Cheng Lee
    • Yin‑Kai Chen
    • Yih‑Jen Hsu
    • Bor‑Ru Lin
  • View Affiliations

  • Published online on: December 27, 2019     https://doi.org/10.3892/or.2019.7449
  • Pages: 549-561
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Niclosamide is an FDA‑approved anthelmintic drug, and may elicit antineoplastic effects through direct STAT3 inhibition, which has been revealed in numerous human cancer cells. Chemotherapy is the standard treatment for advanced esophageal cancers, but also causes severe systemic side effects. The present study represents the first study evaluating the anticancer efficacy of niclosamide in esophageal cancers. Through western blot assay, it was demonstrated that niclosamide suppressed the STAT3 signaling pathway in esophageal adenocarcinoma cells (BE3) and esophageal squamous cell carcinoma cells (CE48T and CE81T). In addition, niclosamide inhibited cell proliferation as determined by 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑ 2‑(4‑sulfophenyl)‑­2H‑tetrazolium)‑5‑(3‑carboxymethoxyphenyl)‑ 2‑(4‑sulfophenyl)‑2H‑tetrazolium (MTS) assay and soft agar colony forming assay, and induced cell apoptosis as determined by Annexin V and PI staining. The induction of p21 and G1 arrest of the cell cycle also was revealed in niclosamide‑treated CE81T cells by qPCR and flow cytometric assays, respectively. Furthermore, in the combination analysis of niclosamide and chemotherapeutic agents by MTS assay, low IC50 values were detected in cells co‑treated with niclosamide, with the exception of cisplatin‑treated CE81T cells. To confirm the results using an apoptosis assay, the apoptotic enhancement of niclosamide was only demonstrated in CE48T cells co‑treated with 5‑FU, cisplatin, or paclitaxel, and in BE3 cells co‑treated with paclitaxel, but not in CE81T cells. These findings indicate a future clinical application of niclosamide in esophageal cancers.
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February 2020
Volume 43 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Lee, M., Chen, Y., Hsu, Y., & Lin, B. (2020). Niclosamide inhibits the cell proliferation and enhances the responsiveness of esophageal cancer cells to chemotherapeutic agents. Oncology Reports, 43, 549-561. https://doi.org/10.3892/or.2019.7449
MLA
Lee, M., Chen, Y., Hsu, Y., Lin, B."Niclosamide inhibits the cell proliferation and enhances the responsiveness of esophageal cancer cells to chemotherapeutic agents". Oncology Reports 43.2 (2020): 549-561.
Chicago
Lee, M., Chen, Y., Hsu, Y., Lin, B."Niclosamide inhibits the cell proliferation and enhances the responsiveness of esophageal cancer cells to chemotherapeutic agents". Oncology Reports 43, no. 2 (2020): 549-561. https://doi.org/10.3892/or.2019.7449