Xinyi Yu1,2, Feng Liu2,3, Liyi Zeng2,4, Fang He1,2, Ruyi Zhang2,5, Shujuan Yan2,5, Zongyue Zeng2,5, Yi Shu2,3,5, Chen Zhao1,2, Xingye Wu1,2, Jiayan Lei1,2, Wenwen Zhang2,6, Chao Yang2,3, Ke Wu2,3, Ying Wu2,7, Liping An2,8, Shifeng Huang1,2, Xiaojuan Ji2,3, Cheng Gong2,9, Chengfu Yuan2,10, Linghuan Zhang2,3, Yixiao Feng1,2, Bo Huang2,4,11, Wei Liu1,2, Bo Zhang2,8, Zhengyu Dai2,12, Xi Wang2,5, Bo Liu1,2, Rex C Haydon2, Hue H Luu2, Hua Gan1, Tong-Chuan He2, Liqun Chen1,2. 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.
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 humanrenal 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 humanRCC.
Authors: John Tam; Therwa Hamza; Bing Ma; Kevin Chen; Greg L Beilhartz; Jacques Ravel; Hanping Feng; Roman A Melnyk Journal: Nat Commun Date: 2018-12-07 Impact factor: 14.919
Authors: Chen Zhao; Nader Taheri Qazvini; Monirosadat Sadati; Zongyue Zeng; Shifeng Huang; Ana Losada De La Lastra; Linghuan Zhang; Yixiao Feng; Wei Liu; Bo Huang; Bo Zhang; Zhengyu Dai; Yi Shen; Xi Wang; Wenping Luo; Bo Liu; Yan Lei; Zhenyu Ye; Ling Zhao; Daigui Cao; Lijuan Yang; Xian Chen; Aravind Athiviraham; Michael J Lee; Jennifer Moriatis Wolf; Russell R Reid; Matthew Tirrell; Wei Huang; Juan J de Pablo; Tong-Chuan He Journal: ACS Appl Mater Interfaces Date: 2019-02-25 Impact factor: 9.229
Authors: Xia Zhao; Bo Huang; Hao Wang; Na Ni; Fang He; Qing Liu; Deyao Shi; Connie Chen; Piao Zhao; Xi Wang; William Wagstaff; Mikhail Pakvasa; Andrew Blake Tucker; Michael J Lee; Jennifer Moriatis Wolf; Russell R Reid; Kelly Hynes; Jason Strelzow; Sherwin H Ho; Tengbo Yu; Jian Yang; Le Shen; Tong-Chuan He; Yongtao Zhang Journal: Am J Transl Res Date: 2021-05-15 Impact factor: 4.060
Authors: Linghuan Zhang; Qing Luo; Yi Shu; Zongyue Zeng; Bo Huang; Yixiao Feng; Bo Zhang; Xi Wang; Yan Lei; Zhenyu Ye; Ling Zhao; Daigui Cao; Lijuan Yang; Xian Chen; Bin Liu; William Wagstaff; Russell R Reid; Hue H Luu; Rex C Haydon; Michael J Lee; Jennifer Moriatis Wolf; Zhou Fu; Tong-Chuan He; Quan Kang Journal: Genes Dis Date: 2019-05-08