title: VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α.
abstract: Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.
authors.affiliation: Department of Urology, Shanghai Tenth People's Hospital, Tongji University, No 301, Yanchang Mid-Road, Shanghai, 200072, China.
authors.forename: Feng-qiang
authors.initials: FQ
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Feng-ping
authors.initials: FP
authors.lastname: Yang
authors.forename: Jianping
authors.initials: J
authors.lastname: Che
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.forename: Guang-chun
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D056464:Histone Deacetylase 2 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014635:Valproic Acid; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2