Full Text | PDF

Share on facebook Share on tweeters Share on linkedin Share on googleplus

J Cancer 2024; 15(13):4406-4416. doi:10.7150/jca.95682 This issue Cite

Research Paper

Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity

Wanjin Jiang1,2, Xiaonan Yang1, Xiao Han1, Ruijia Gan1, Hongting Hua1, Dongyu Si1, Fuqin Sun2, Zhimin Ding5, Xinbei Zhu6, Qi Yang4✉, Huabing Zhang3✉, Chaobing Gao1✉

1. Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
2. Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
3. Department of Biochemistry & Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
4. Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
5. Department of Otorhinolaryngology Head and Neck Surgery, Xuancheng People's Hospital, Xuancheng, 242000, China.
6. Department of Otorhinolaryngology Head and Neck Surgery, The Second People's Hospital of Hefei, Hefei, 230011, China.

✉ Corresponding authors: Qi Yang, Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China, E-mail: yangqiedu.cn; Huabing Zhang, Ph.D, Department of Biochemistry & Molecular Biology, School More

Citation:
Jiang W, Yang X, Han X, Gan R, Hua H, Si D, Sun F, Ding Z, Zhu X, Yang Q, Zhang H, Gao C. Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity. J Cancer 2024; 15(13):4406-4416. doi:10.7150/jca.95682. https://www.jcancer.org/v15p4406.htm
Other styles

File import instruction

Abstract

Graphic abstract

Background: Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health. Niclosamide is an anti-helminthic drug that has received FDA approval. In drug repurposing screens, niclosamide was found to inhibit proliferative activity for a range of tumor types. Its functional effects in HNSC, however, have yet to be established.

Methods: MTT and colony formation assays were used to explore the impact of niclosamide on the proliferation of HNSC cells, while wound healing and Transwell assays were employed to assess migration and invasivity. Flow cytometry and Western immunoblotting were respectively used to assess cellular apoptosis and protein expression patterns. An HNSC xenograft tumor model system was used to evaluate the in vivo antitumor activity of niclosamide, and immunofluorescent staining was employed to assess cleaved Caspase3 and Ki67 expression. The ability of niclosamide to prevent metastatic progression in vivo was assessed with a model of pulmonary metastasis.

Results: These analyses revealed the ability of niclosamide to suppress HNSC cell migration, proliferation, and invasivity in vitro while promoting apoptotic death. From a mechanistic perspective, this drug suppressed Stat3 phosphorylation and β-catenin expression, while increasing cleaved Caspase3 levels in HNSC cells and reducing Bcl-2 levels. Importantly, this drug was able to suppress in vivo tumor growth and pulmonary metastasis formation, with immunofluorescent staining confirming that it reduced Ki67 levels and increased cleaved Caspase3 content.

Conclusion: In conclusion, these analyses highlight the ability of niclosamide to inhibit HNSC cell migration and proliferative activity while provoking apoptotic death mediated via p-Stat3 and β-catenin pathway inactivation. Niclosamide thus holds promise for repurposing as a candidate drug for the more effective clinical management of HNSC.

Keywords: Head and neck squamous cell carcinoma, niclosamide, Stat3, β-catenin, apoptosis

Citation styles

APA
Jiang, W., Yang, X., Han, X., Gan, R., Hua, H., Si, D., Sun, F., Ding, Z., Zhu, X., Yang, Q., Zhang, H., Gao, C. (2024). Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity. Journal of Cancer, 15(13), 4406-4416. https://doi.org/10.7150/jca.95682.

ACS
Jiang, W.; Yang, X.; Han, X.; Gan, R.; Hua, H.; Si, D.; Sun, F.; Ding, Z.; Zhu, X.; Yang, Q.; Zhang, H.; Gao, C. Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity. J. Cancer 2024, 15 (13), 4406-4416. DOI: 10.7150/jca.95682.

NLM
Jiang W, Yang X, Han X, Gan R, Hua H, Si D, Sun F, Ding Z, Zhu X, Yang Q, Zhang H, Gao C. Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity. J Cancer 2024; 15(13):4406-4416. doi:10.7150/jca.95682. https://www.jcancer.org/v15p4406.htm

CSE
Jiang W, Yang X, Han X, Gan R, Hua H, Si D, Sun F, Ding Z, Zhu X, Yang Q, Zhang H, Gao C. 2024. Treatment of HNSC and pulmonary metastasis using the anti-helminthic drug niclosamide to modulate Stat3 signaling activity. J Cancer. 15(13):4406-4416.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use