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Cell Physiol Biochem. 2018;47(3):957-971. doi: 10.1159/000490140. Epub 2018 May 24.

Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells.

Yu X1,2, Liu F2,3, Zeng L2,4, He F1,2, Zhang R2,5, Yan S2,5, Zeng Z2,5, Shu Y2,3,5, Zhao C1,2, Wu X1,2, Lei J1,2, Zhang W2,6, Yang C2,3, Wu K2,3, Wu Y2,7, An L2,8, Huang S1,2, Ji X2,3, Gong C2,9, Yuan C2,10, Zhang L2,3, Feng Y1,2, Huang B2,4,11, Liu W1,2, Zhang B2,8, Dai Z2,12, Wang X2,5, Liu B1,2, Haydon RC2, Luu HH2, Gan H1, He TC2, Chen L1,2.

Author information

1
Departments of Nephrology, Orthopaedic Surgery, Cardiology, General Surgery, Plastic Surgery and Clinical Laboratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
2
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA.
3
Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital of Chongqing Medical University, Chongqing, China.
4
Department of Infection Control, Zhuzhou Central Hospital, and the Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Zhuzhou, China.
5
Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
6
Department of Obstetrics and Gynecology, the Affiliated University-Town Hospital, Chongqing Medical University, Chongqing, China.
7
Department of Immunology and Microbiology, Beijing University of Chinese Medicine, Beijing, China.
8
Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery, the Second Hospital of Lanzhou University, Lanzhou, China.
9
Department of Surgery, the Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China.
10
Department of Biochemistry and Molecular Biology, China Three Gorges University School of Medicine, Yichang, China.
11
Department of Clinical Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
12
Department of Orthopaedic Surgery, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.

Abstract

BACKGROUND/AIMS:

As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation.

METHODS:

Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model.

RESULTS:

We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation.

CONCLUSIONS:

Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC.

KEYWORDS:

Drug repurposing; Kidney cancer; Metastatic renal cancer; Niclosamide; Renal cell carcinoma; Targeted therapy

PMID:
29843133
DOI:
10.1159/000490140
[Indexed for MEDLINE]
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