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

被引：31

作者：

Yu, Xinyi ^{[1
,2
,3
,4
,5
,6
,7
]}

Liu, Feng ^{[7
,8
]}

Zeng, Liyi ^{[7
,9
,10
]}

He, Fang ^{[1
,2
,3
,4
,5
,6
,7
]}

Zhang, Ruyi ^{[7
,11
,12
]}

Yan, Shujuan ^{[7
,11
,12
]}

Zeng, Zongyue ^{[7
,11
,12
]}

Shu, Yi ^{[7
,8
,11
,12
]}

Zhao, Chen ^{[1
,2
,3
,4
,5
,6
,7
]}

Wu, Xingye ^{[1
,2
,3
,4
,5
,6
,7
]}

Lei, Jiayan ^{[1
,2
,3
,4
,5
,6
,7
]}

Zhang, Wenwen ^{[7
,13
]}

Yang, Chao ^{[7
,8
]}

Wu, Ke ^{[7
,8
]}

Wu, Ying ^{[7
,14
]}

An, Liping ^{[7
,15
,16
]}

Huang, Shifeng ^{[1
,2
,3
,4
,5
,6
,7
]}

Ji, Xiaojuan ^{[7
,8
]}

Gong, Cheng ^{[7
,17
]}

Yuan, Chengfu ^{[7
,18
]}

Zhang, Linghuan ^{[7
,8
]}

Feng, Yixiao ^{[1
,2
,3
,4
,5
,6
,7
]}

Huang, Bo ^{[7
,9
,10
,19
]}

Liu, Wei ^{[1
,2
,3
,4
,5
,6
,7
]}

Zhang, Bo ^{[7
,15
,16
]}

Dai, Zhengyu ^{[7
,20
]}

Wang, Xi ^{[7
,11
,12
]}

Liu, Bo ^{[1
,2
,3
,4
,5
,6
,7
]}

Haydon, Rex C. ^{[7
]}

Luu, Hue H. ^{[7
]}

Gan, Hua ^{[1
,2
,3
,4
,5
,6
]}

He, Tong-Chuan ^{[7
]}

Chen, Liqun ^{[1
,2
,3
,4
,5
,6
,7
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Chongqing, Peoples R China

[3] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China

[4] Chongqing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Chongqing, Peoples R China

[5] Chongqing Med Univ, Affiliated Hosp 1, Dept Plast Surg, Chongqing, Peoples R China

[6] Chongqing Med Univ, Affiliated Hosp 1, Dept Clin Lab Med, Chongqing, Peoples R China

[7] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Mol Oncol Lab, Chicago, IL 60637 USA

[8] Chongqing Med Univ, Childrens Hosp, Stem Cell Biol & Therapy Lab, Minist Educ,Key Lab Child Dev & Disorders, Chongqing, Peoples R China

[9] Cent S Univ, Zhuzhou Cent Hosp, Dept Infect Control, Zhuzhou, Peoples R China

[10] Cent S Univ, Xiangya Med Coll, Affiliated Zhuzhou Hosp, Zhuzhou, Peoples R China

[11] Chongqing Med Univ, Key Lab Diagnost Med, Minist Educ, Chongqing, Peoples R China

[12] Chongqing Med Univ, Sch Lab Med, Chongqing, Peoples R China

[13] Chongqing Med Univ, Affiliated Univ Town Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China

[14] Beijing Univ Chinese Med, Dept Immunol & Microbiol, Beijing, Peoples R China

[15] Lanzhou Univ, Key Lab Orthopaed Surg Gansu Prov, Hosp 2, Lanzhou, Gansu, Peoples R China

[16] Lanzhou Univ, Dept Orthopaed Surg, Hosp 2, Lanzhou, Gansu, Peoples R China

[17] Wuhan Univ, Dept Surg, Zhongnan Hosp, Wuhan, Hubei, Peoples R China

[18] China Three Gorges Univ, Dept Biochem & Mol Biol, Sch Med, Yichang, Peoples R China

[19] Nanchang Univ, Affiliated Hosp 2, Dept Clin Lab Med, Nanchang, Jiangxi, Peoples R China

[20] Chongqing Hosp Tradit Chinese Med, Dept Orthopaed Surg, Chongqing, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2018年 / 47卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Niclosamide; Renal cell carcinoma; Kidney cancer; Drug repurposing; Metastatic renal cancer; Targeted therapy; HUMAN OSTEOSARCOMA GROWTH; SUPPRESSES TUMOR-GROWTH; WNT/BETA-CATENIN PATHWAY; OVARIAN-CANCER; KIDNEY CANCER; STEM-CELLS; RESISTANCE; INHIBITION; THERAPY; DIFFERENTIATION;

D O I：

10.1159/000490140

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. (C) 2018 The Author(s) Published by S. Karger AG, Basel

引用

页码：957 / 971

页数：15

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