title: A novel sphingosine kinase 1 inhibitor (SKI-5C) induces cell death of Wilms' tumor cellsin vitroandin vivo.
abstract: Sphingosine kinase 1 (SphK1) is over-expressed in many cancers and therefore serves as a biomarker for cancer prognosis. SKI-5C is a new SphK1 inhibitor, and until now its molecular function in Wilms' tumor cells remained unknown. Here, using CCK-8 and nude mice experiments we assessed cell growth in Wilms' tumor cell lines (SK-NEP-1 and G401)in vitroandin vivo. We demonstrated that SphK1 is highly expressed in SK-NEP-1 and G401 cells, and through annexin V/propidium iodide staining and flow cytometry analysis, we detected cell apoptosis. Treatment with SKI-5C inhibited proliferation and induced apoptosis of SK-NEP-1 and G401 cells in a dose-dependent manner. Moreover, SKI-5C treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice, with few side effects. Our microarray analysis revealed that SKI-5C-treated SK-NEP-1 cells mostly downregulated PRKACA and significantly inhibited phosphorylation of ERK1/2 and NF-κB p65. These results imply that SKI-5C induces apoptosis of SK-NEP-1 cells through the PRKACA/MAPK/NF-κB pathway. While, further research is required to determine the underlying details, these results provide new clues for the molecular mechanism of cell death induced by SKI-5C and suggest that SKI-5C may act as new candidate drug for Wilms' tumor.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Tao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Xu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Du
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Ren
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAM-SU Genomic Resource Center, Soochow University Suzhou, China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: He
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
keywords: SKI-5C; Wilms’ tumor; cell death; sphingosine kinase 1 (SphK1)