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

Cellular Physiology and Biochemistry - Tập 47 Số 3 - Trang 957-971 - 2018
Xinyi Yu1,2, Feng Liu2,3, Liyi Zeng4,2, Fang He1,2, Ruyi Zhang5,2, Shujuan Yan5,2, Zongyue Zeng5,2, Yi Shu5,2,3, Chen Zhao1,2, Xingye Wu1,2, Jiayan Lei1,2, Wenwen Zhang6,2, Chao Yang2,3, Ke Wu2,3, Ying Wu7,2, Liping An8, Shifeng Huang1,2, Xiaojuan Ji2,3, Gong Cheng9,2, Chengfu Yuan10,2, Linghuan Zhang2,3, Yixiao Feng1,2, Bo Huang11,4,2, Wei Liu1,2, Bo Zhang12,2, Zhengyu Dai13,2, Xi Wang5,2, Bo Liu1,2, Rex C. Haydon2, Hue H. Luu2, Hua Gan1, Tong‐Chuan He2, Li‐Qun Chen1,2
1Departments of Nephrology, Orthopaedic Surgery, Cardiology, General Surgery, Plastic Surgery and Clinical Laboratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
3Stem 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
4Department of Infection Control, Zhuzhou Central Hospital, and the Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Zhuzhou, China
5Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
6Department of Obstetrics and Gynecology, the Affiliated University-Town Hospital, Chongqing Medical University, Chongqing, China
7Department of Immunology and Microbiology, Beijing University of Chinese Medicine, Beijing, China
8Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery, the Second Hospital of Lanzhou University, Lanzhou, China.; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA.
9Department of Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China
10Department of Biochemistry and Molecular Biology, China Three Gorges University School of Medicine, Yichang, China
11Department of Clinical Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
12Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery, the Second Hospital of Lanzhou University, Lanzhou, China
13Department of Orthopaedic Surgery, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China

Tóm tắt

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.

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