title: Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation.
abstract: There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H2DCF-DA to detect intracellular ROS, siRNA to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP.
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Cunjin
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Guowen
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Zhanhong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China. Electronic address: hudmsdfey@sina.com.
authors.forename: Duanmin
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China. Electronic address: baojjsdfey@sina.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Bao
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D034741:RNA, Small Interfering; C486715:TXNIP protein, human; D011345:Fenofibrate
keywords: Apoptosis; Fenofibrate; Neuroblastoma; Oxidative stress; SHSY5Y; TXNIP