title: Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma.
abstract: Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.
authors.affiliation: Faculty of Integrative Medicine, Traditional Chinese Medicine University of Hunan, Changsha, People's Republic of China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Liu
authors.forename: Y M
authors.initials: YM
authors.lastname: Sun
authors.forename: D F
authors.initials: DF
authors.lastname: Tian
authors.forename: Y C
authors.initials: YC
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.forename: C Q
authors.initials: CQ
authors.lastname: Ling
authors.forename: S H
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D054778:NM23 Nucleoside Diphosphate Kinases; D001599:Berberine; C517938:NME1 protein, human