title: Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma.
abstract: Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo. It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated-Src, phosphorylated-FAK, and expression of matrix metalloproteinase (MMP) -2, MMP-9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid-derived suppressor cells (MDSCs). These findings suggested that nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma.
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: College of agricultural and life sciences, University of Wisconsin-Madison, Madison, WI53706, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.|Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Tiantao
authors.initials: T
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.|Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Cuiting
authors.initials: C
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, 404100, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Ningyu
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Luoting
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008546:Melanoma, Experimental; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009362:Neoplasm Metastasis; D009581:Nitrofurans / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D062385:Hydroxybenzoates; D009581:Nitrofurans; C013150:nifuroxazide
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